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Fibroblast Proliferation (fibroblast + proliferation)
Selected AbstractsAttenuation of Bleomycin-Induced Lung Fibrosis by Oxymatrine Is Associated with Regulation of Fibroblast Proliferation and Collagen Production in Primary CultureBASIC AND CLINICAL PHARMACOLOGY & TOXICOLOGY, Issue 3 2008Xiaohong Chen Oxymatrine is an alkaloid extracted from the Chinese herb Sophora japonica (Sophora flavescens Ait.) with capacities of anti-inflammation, inhibition of immune reaction, antivirus, protection against acute lung injury and antihepatic fibrosis. In this study, the effect of oxymatrine on pulmonary fibrosis was investigated using a bleomycin-induced pulmonary fibrosis mouse model. The results showed that bleomycin challenge provoked severe pulmonary fibrosis with marked increase in hydroxyproline content of lung tissue and lung fibrosis fraction, which was prevented by oxymatrine in a dose-dependent manner. In addition, bleomycin injection resulted in a marked increase of myeloperoxidase activity and malondialdehyde level that was attenuated by oxymatrine. Administration of oxymatrine inhibited the proliferation of murine lung fibroblasts, arrested the cells at G0/G1 phase and reduced the expression of cell cycle regulatory protein, cyclin D1 in vitro. Furthermore, the steady-state production of collagen and the expression of ,1(I) pro-collagen and ,2(I) pro-collagen mRNA in fibroblasts were inhibited by oxymatrine in a dose-dependent manner. These results suggested that oxymatrine may attenuate pulmonary fibrosis induced by bleomycin in mice, partly through inhibition of inflammatory response and lipid peroxidation in lung induced by bleomycin and reduction of fibroblast proliferation and collagen synthesis. [source] Influence of TiO2 Nanoparticles Incorporated into Elastomeric Polyesters on their Biocompatibility In Vitro and In VivoADVANCED ENGINEERING MATERIALS, Issue 11 2009Miroslawa El-Fray Abstract Fibroblasts proliferation and apoptosis as well as tissue response after implantation of elastomers containing nanocrystalline TiO2 were investigated in the present in vitro and in vivo study. Materials investigated were soft poly(aliphatic/aromatic-ester) multiblock thermoplastic elastomers with poly(ethylene terephthalate) (PET) hard segments and dimerized linoleic acid (DLA) soft segments, respectively, containing 0.2,wt% TiO2 nanoparticles. An investigation of the influence of TiO2 nanoparticles incorporated into polymeric material on in vitro biocompatibility revealed enhanced cell proliferation and diminished number of necrotic and apoptotic cells as compared to nanoparticles-free polymer. Implantation tests indicated that the observed tissue changes were similar to those observed with medical-grade silicone elastomer, no evidence of contact necrosis being observed. The unchanged morphology of rat liver hepatocytes and the lack of parenchymal necrosis also indicated that exposure to the material containing TiO2 nanoparticles, did not cause any cytotoxic reactions. The present study, thus, showed that elastomeric polyester containing TiO2 nanoparticles are interesting biomimetic constructs for improved tissue regeneration. [source] Comparison of acidic fibroblast growth factor on collagen carrier with calcium hydroxide as pulp capping agents in monkeysDENTAL TRAUMATOLOGY, Issue 5 2007Zhimei Li Abstract,,, Acidic fibroblast growth factor (aFGF) has been shown to facilitate wound healing by stimulating fibroblast proliferation and angiogenesis. It has also been reported to possess a powerful anti-apoptotic function This study compared the histological pulp responses to aFGF on collagen carrier and Ca(OH)2 placed on the mechanically exposed dental pulp in monkeys at two observation periods. Thirty-six teeth with pulp exposures were distributed into three groups according to the capping agents used prior to application of the coronal seal: collagen-based matrix carrier (group 1), aFGF on the collagen-based matrix carrier (group 2) and aqueous calcium hydroxide [Ca(OH)2] paste (group 3). Specimens were harvested at 6 and 13 weeks postoperatively and prepared for hematoxylin and eosin, and Gram staining. Histological qualitative evaluation of pulp responses were performed under the light microscope following criteria modified from Cox et al. (17) and Hu et al. (18). Semi-quantitative analysis was also carried out using Kruskal,Wallis and Mann,Whitney U -tests. There was neither negligible inflammatory infiltrates with no bacteria present in the three groups at both timings, nor was there any significant difference in the soft tissue organization among the three groups at or between the 6- and 13-week observation periods. At 6 weeks, the hard tissue barrier produced by Ca(OH)2 group (1.040 ± 0.089) was significantly more superior than aFGF/collagen carrier group (1.930 ± 0.825) (P = 0.030) as well as collagen carrier group (3.142 ± 1.069, P = 0.018). At 13 weeks, both aFGF/collagen carrier group (1.214 ± 0.485) and the collagen carrier group (1.457 ± 0.814) produced significantly better hard tissue barrier (P = 0.040 and P = 0.017, respectively) than earlier timing. However, these two groups did not induce significantly improved hard tissue barrier compared to that produced by aqueous Ca(OH)2 paste which stimulated matrix secretion in a polar tubular dentin-like pattern. [source] Hydrogen Peroxide and Wound Healing: A Theoretical and Practical Review for Hair Transplant SurgeonsDERMATOLOGIC SURGERY, Issue 6 2008SARA WASSERBAUER MD BACKGROUND In most hair restoration practices, hydrogen peroxide has been routinely used to remove blood during and after hair transplant surgery. In other specialties, hydrogen peroxide is also used in these ways: wound cleaning, prevention of infection, hemostasis, and removal of debris. Despite its widespread use, there are still concerns and controversy about the potential toxic effect of hydrogen peroxide. OBJECTIVE The objective was to review all available literature including in vivo and in vitro effects of hydrogen peroxide, as well as general wound healing research. MATERIAL AND METHODS Literature up to and including the past three decades was investigated. RESULTS Two pilot studies were found, and there are not enough data examining the real impact of using hydrogen peroxide in hair transplant surgery. In other specialties, H2O2 appears to have positive effects, such as stimulation of vascular endothelial growth factor, induction of fibroblast proliferation, and collagen, or negative effects, such as cytotoxicity, inhibition of keratinocyte migration, disruption of scarless fetal wound repair, and apoptosis. CONCLUSIONS There are not enough data in hair restoration surgery about the use of hydrogen peroxide, and it is unknown and unclear what the optimum dilution should be. Positive and negative effects were found in other specialties. Further studies are recommended. [source] Augmentation of all- trans -retinoic acid concentration in plasma by preventing inflammation responses induced by atRA-loaded microspheres with concurrent treatment of dexamethasoneDRUG DEVELOPMENT RESEARCH, Issue 4 2004Kyeongsoon Park Abstract All- trans retinoic acid (atRA)-loaded microspheres severely induce inflammatory responses after microsphere implantation. Fibroblasts and a thick band of fibrous capsule resulting from the inflammatory responses could hamper drug permeation to the bloodstream because fibroblasts actively metabolize atRA into polar metabolites and the thick fibrous capsule acts as a diffusion barrier. In the present study, we investigated whether the fibroblast proliferation and collagen deposition induced by atRA released from microspheres might affect the atRA concentration in plasma and atRA metabolism with or without treatment of dexamethasone as an anti-inflammatory drug. After subcutaneous injection of atRA-loaded microspheres in rats, it was observed that atRA-loaded microspheres induced severe inflammatory responses and stimulated fibroblast proliferation and collagen deposition in fibrous capsules. On the other hand, the orally treated dexamethasone effectively prevented inflammatory responses in a dose-dependent manner and suppressed about 49% of the number of fibroblasts and collagen deposition in fibrous capsules at 14 days. In addition, after the treatment of dexamethasone, the atRA concentration in plasma was increased, and its metabolism was decreased approximately by 40% at 7 days, compared to the group treated alone with atRA-loaded microspheres. In conclusion, the concurrent treatment of dexmethasone with atRA-loaded microspheres could prevent inflammatory responses and metabolism of atRA, thereby maintaining the atRA concentration in plasma for longer periods in the therapeutic range. Drug Dev. Res. 61:197,206, 2004. © 2004 Wiley-Liss, Inc. [source] Effect of parathyroid hormone-related protein on fibroblast proliferation and collagen metabolism in human skinEXPERIMENTAL DERMATOLOGY, Issue 4 2002Emanuela Maioli Abstract: The parathyroid hormone-related protein (PTHrp), structurally similar to the parathyroid hormone (PTH) in its NH2 -terminal part, was first identified as a tumour-derived peptide responsible for a paraneoplastic syndrome known as humoral hypercalcemia of malignancy. The PTHrp gene is expressed not only in cancer but also in normal tissues during adult and/or fetal life, where it plays predominantly paracrine and/or autocrine roles. In the skin PTHrp produced by keratinocytes acts on fibroblasts by complex cooperative circuits involving cytokines and growth factors. In this report, we studied the direct effects of synthetic PTHrp 1,40 on proliferation and collagen synthesis and matrix metalloproteinase-2 (MMP-2) activity in cultures of fibroblasts isolated from normal human skin. Fibroblasts exposure to varying doses of PTHrp for 48 h, significantly and dose-dependently inhibited proliferation evaluated by [3H]-thymidine incorporation into DNA. A dose-dependent stimulation of cAMP released into the medium was concomitantly observed. In contrast, PTHrp had no effect on collagen synthesis evaluated either by [3H]-proline incorporation or by radioimmunoassay (RIA) of the carboxyterminal fragment of type I procollagen (PICP). MMP-2 activity, evaluated by quantitative zymographic analysis, was significantly increased by PTHrp treatment at doses of 160 and 320 nM. These findings indicate that PTHrp may play a role in normal dermal physiology by controlling both fibroblast proliferation and extracellular matrix degradation. [source] Stimulation of fibroblast proliferation by neokyotorphin requires Ca2+ influx and activation of PKA, CaMK II and MAPK/ERKFEBS JOURNAL, Issue 2 2007Olga V. Sazonova Neokyotorphin [TSKYR, hemoglobin ,-chain fragment (137,141)] has previously been shown to enhance fibroblast proliferation, its effect depending on cell density and serum level. Here we show the dependence of the effect of neokyotorphin on cell type and its correlation with the effect of protein kinase A (PKA) activator 8-Br-cAMP, but not the PKC activator 4,-phorbol 12-myristate, 13-acetate (PMA). In L929 fibroblasts, the proliferative effect of neokyotorphin was suppressed by the Ca2+L -type channel inhibitors verapamil or nifedipine, the intracellular Ca2+ chelator 1,2-bis(2-aminophenoxy)ethane- N,N,N,,N, - tetraacetic acid acetoxymethyl ester, kinase inhibitors H-89 (PKA), KN-62 (Ca2+/calmodulin-dependent kinase II) and PD98059 (mitogen-activated protein kinase). The proliferative effect of 8-Br-cAMP was also suppressed by KN-62 and PD98059. PKC suppression (downregulation with PMA or inhibition with bisindolylmaleimide XI) did not affect neokyotorphin action. The results obtained point to a cAMP-like action for neokyotorphin. [source] Synovial mast cells: role in acute and chronic arthritisIMMUNOLOGICAL REVIEWS, Issue 1 2007Peter A. Nigrovic Summary:, Mast cells reside in the normal synovium and increase strikingly in number in rheumatoid arthritis and other joint diseases. Given the broad spectrum of activity of this lineage, it has for decades been considered probable that mast cells are involved in the pathophysiology of synovitis. Recent work in murine arthritis has substantiated this suspicion, showing that mast cells can contribute importantly to the initiation of inflammatory arthritis. However, the role of the greatly expanded population of synovial mast cells in established arthritis remains unknown. Here we review the current understanding of mast cell function in acute arthritis and consider the potentially important influence of this cell on key processes within the chronically inflamed synovium, including leukocyte recruitment and activation, fibroblast proliferation, angiogenesis, matrix remodeling, and injury to collagen and bone. We also consider recent evidence supporting an immunomodulatory or anti-inflammatory role for mast cells as well as pharmacologic approaches to the mast cell as a therapeutic target in inflammatory arthritis. [source] Serum bFGF and VEGF correlate respectively with bowel wall thickness and intramural blood flow in Crohn's diseaseINFLAMMATORY BOWEL DISEASES, Issue 5 2004Dr. Antonio Di Sabatino MD Abstract Serum levels of basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF),two factors known to promote tissue repair, fibroblast proliferation, and angiogenesis,were measured in Crohn's disease patients and correlated with bowel wall thickness (BWT), measured by conventional grey scale ultrasonography, and with the ileal intramural vessel flow, measured by contrast-enhanced color Doppler imaging. Serum samples were obtained from 25 patients with active Crohn's disease and 22 healthy volunteers, all sex- and age-matched. Serum bFGF and VEGF levels were measured by ELISA assay. All the patients were examined with conventional transabdominal bowel sonography. Color Doppler of the intramural enteric vessels was then performed after the intravenous injection of Levovist, a galactose-based sonographic contrast agent. In Crohn's disease patients, serum bFGF and VEGF were significantly higher compared with healthy volunteers. A positive correlation between serum bFGF and BWT and between serum VEGF and color Doppler signal intensity was found. The raised serum bFGF levels in Crohn's disease patients with intestinal strictures compared with patients with other phenotypes (fistulizing, inflammatory), together with the correlation observed between serum bFGF and BWT, suggests a possible involvement of bFGF in the process of transmural fibrogenesis in Crohn's disease. The higher levels of VEGF in those patients with increased intramural blood flow suggests that VEGF may be considered a marker of angiogenesis in this condition. [source] S100A6 (calcyclin) deficiency induces senescence-like changes in cell cycle, morphology and functional characteristics of mouse NIH 3T3 fibroblastsJOURNAL OF CELLULAR BIOCHEMISTRY, Issue 3 2010omnicki, ukasz P. S Abstract S100A6 (calcyclin) is a calcium binding protein with two EF-hand structures expressed mostly in fibroblasts and epithelial cells. We have established a NIH 3T3 fibroblast cell line stably transfected with siRNA against S100A6 to examine the effect of S100A6 deficiency on non-transformed cell physiology. We found that NIH 3T3 fibroblasts with decreased level of S100A6 manifested altered cell morphology and proliferated at a much slower pace than the control cells. Cell cycle analysis showed that a large population of these cells lost the ability to respond to serum and persisted in the G0/G1 phase. Furthermore, fibroblasts with diminished S100A6 level exhibited morphological changes and biochemical features of cellular senescence as revealed by ,-galactosidase and gelatinase assays. Also, S100A6 deficiency induced changes in the actin cytoskeleton and had a profound impact on cell adhesion and migration. Thus, we have shown that the S100A6 protein is involved in multiple aspects of fibroblast physiology and that its presence ensures normal fibroblast proliferation and function. J. Cell. Biochem. 109: 576,584, 2010. © 2009 Wiley-Liss, Inc. [source] Toothbrushing promotes gingival fibroblast proliferation more effectively than removal of dental plaqueJOURNAL OF CLINICAL PERIODONTOLOGY, Issue 9 2002Masazumi Horiuchi Abstract Objectives: Removal of dental plaque is an essential element of periodontal treatment. However, there have also been studies of the effects of the mechanical stimulation provided by toothbrushing on gingival host-defense mechanisms. The aim of the study was to evaluate the effects of toothbrushing on gingival fibroblast proliferation in dogs over time, compared to effects of plaque removal without brushing. Methods: The mouths of six mongrel dogs were divided into four quadrants: two for daily toothbrushing, and two for daily plaque removal with a curette. After 1, 3 and 5 weeks of treatment, histometrical analyses were performed to assess inflammatory cell infiltration, proliferating cell nuclear antigen (PCNA)-positive fibroblasts, procollagen type I-positive fibroblasts in the subepithelial connective tissue of junctional epithelium. Results: Toothbrushing increased the number of PCNA-positive fibroblasts in the first week, increased the number of type I procollagen-positive fibroblasts at the fifth week, and reduced inflammatory cell infiltration at the third week. Conclusion: These findings suggest that mechanically stimulated fibroblasts begin proliferating within a week, and this cell division results in an increased number of fibroblasts at the third week. It takes 5 weeks before differences in collagen synthesis between brushing and plaque removal areas are detectable. Zusammenfassung Die Proliferation der gingivalen Fibroblasten wird durch Zähneputzen wirkungsvoller gefördert als durch Plaqueentfernung Ziele: Die Entfernung von Zahnplaque ist ein essenzieller Bestandteil der Parodontalbehandlung. Es gibt jedoch auch Studien über die Wirkung einer durch Zähneputzen bewirkten mechanischen Stimulation der gingivalen Abwehrmechanismen. Ziel dieser Studie war es, bei Hunden die Wirkung des Zähneputzen auf die Proliferation der gingivalen Fibroblasten über eine gewisse Zeit zu untersuchen und mit der Wirkung einer Plaqueentfernung ohne Zähneputzen zu vergleichen. Methoden: Das Maul von 6 Mischlingshunden wurde in vier Quadranten unterteilt: zwei mit täglichem Zähneputzen und zwei mit täglicher Plaqueentfernung mittels Kürette. 1, 3 und 5 Wochen nach der Behandlung wurden histometrische Analysen durchgeführt um das entzündliche Zellinfiltrat, die proliferierenden Cell-Nuclear-Antigen (PCNA)-positiven Fibroblasten und die Prokollagen-I-positiven Fibroblasten des subgingivalen Bindegewebes des Saumepithels zu bestimmen. Ergebnisse: Zähneputzen erhöhte in der ersten Woche die Anzahl der PCNA-positiven Fibroblasten, erhöhte bis zur fünften Woche die Anzahl der Type-I-Prokollagen-positiven Fibroblasten und reduzierte das entzündliche Zellinfiltrat bis zur dritten Woche. Schlussfolgerung: Diese Ergebnisse lassen annehmen, dass mechanisch stimulierte Fibroblasten während einer Woche zu proliferieren beginnen und diese Zellteilung eine erhöhte Anzahl von Fibroblasten in der dritten Woche zum Ergebnis hat. Es dauert fünf Wochen bevor zwischen den Bereichen mit Zähneputzen und Plaqueentfernung Unterschiede in der Kollagensynthese nachweisbar sind. Résumé Le brossage dentaire favorise la prolifération des fibroblastes gingivaux d'une manière plus efficace que l'enlèvement de la plaque dentaire L'enlèvement de la plaque dentaire est un élément essentiel dans le traitement parodontal. Cependant, des études ont été menées sur les effets de la stimulation mécanique produit par le brossage dentaire sur les mécanismes de défense de l'hôte au niveau gingival. Le but de l'étude présente a été d'évaluer les effets du brossage dentaire sur la prolifération des fibroblastes gingivaux chez les chiens dans le temps, comparés aux effets de l'enlèvement de la plaque dentaire sans brossage. Les bouches de six chiens bâtards ont été divisés en quatre quadrants : deux pour un brossage dentaire journalier et deux pour l'enlèvement journalier de la plaque à l'aide d'une curette. Après une, trois et cinq semaines de traitement, les analyses histométriques ont été effectuées pour évaluer l'infiltration cellulaire inflammatoire, les fibroblastes positifs à l'antigène du noyau cellulaire proliférant (PCNA), les fibroblastes positifs au procollagène-I dans le tissu conjonctif sous-épithélial de l'épithélium de jonction. Le brossage dentaire augmentait le nombre de fibroblastes positifs (PCNA) durant la première semaine, augmentait le nombre de fibroblastes positifs au collagène type-1 à la cinquième semaine et réduisait l'infiltration cellulaire inflammatoire à la troisième semaine. Ces découvertes suggèrent que les fibroblastes stimulés mécaniquement commencent à proliférer en une semaine, et cette division cellulaire abouti en un nombre plus important de fibroblastes à la troisième semaine. Il faut attendre cinq semaines avant que des différences dans la synthèse du collagène entre les zones de brossage et d'enlèvement de la plaque dentaire ne soient détectables. [source] Cigarette smoke condensate affects the collagen-degrading ability of human gingival fibroblastsJOURNAL OF PERIODONTAL RESEARCH, Issue 6 2009W. Zhang Background and Objective:, Cigarette smoke condensate, the particulate matter of cigarette smoke, is composed of thousands of chemicals, including nicotine. Cigarette smoking is a risk factor for periodontal disease. This study investigated the influence of cigarette smoke condensate on the collagen-degrading ability of human gingival fibroblasts and its mechanism. Material and Methods:, Human gingival fibroblasts were exposed for 72 h to various concentrations of total particulate matter cigarette smoke condensate. Cell proliferation and cytotoxicity were evaluated using water-soluble tetrazolium-1 and lactate dehydrogenase, respectively. The collagen-degrading ability of human gingival fibroblasts was evaluated in collagen-coated six-well plates. Conditioned media and membrane extracts were collected for zymography and western blot analyses of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs). Results:, Cell proliferation decreased and cytotoxicity increased in human gingival fibroblasts with increasing concentrations of cigarette smoke condensate. Cell proliferation decreased by more than 50% (p < 0.05) when the concentrations of total particulate matter cigarette smoke condensate were above 200 ,g/mL, and cytotoxicity increased to more than 30% (p < 0.05) when the concentrations of total particulate matter cigarette smoke condensate were above 400 ,g/mL. Cigarette smoke condensate increased the collagen-degrading ability of human gingival fibroblasts, especially at a concentration of 100 ,g/mL (1.5-fold increase, p < 0.05) compared with the control. Cigarette smoke condensate increased the production of proMMP-1, proMMP-2, MMP-14 and TIMP-1, and decreased the production of TIMP-2, in conditioned media. Furthermore, compared with the control group, cigarette smoke condensate increased the production of MMP-2, MMP-14 and TIMP-2 in membrane extracts, especially at concentrations of 50,100 ,g/mL. Conclusion:, Cigarette smoke condensate affects human gingival fibroblast proliferation and is toxic at total particulate matter cigarette smoke condensate concentrations of , 400 ,g/mL. Cigarette smoke condensate can increase the collagen-degrading ability of human gingival fibroblasts by altering the production and localization of MMPs and TIMPs. [source] Close dependence of fibroblast proliferation on collagen scaffold matrix stiffnessJOURNAL OF TISSUE ENGINEERING AND REGENERATIVE MEDICINE, Issue 2 2009E. Hadjipanayi Abstract Human dermal fibroblasts (HDFs) in free-floating collagen matrices show minimal proliferation, although this may increase when the matrix is ,under tension'. We have investigated the detailed mechanics underlying one of the possible controls of this important cell behaviour, in particular the hypothesis that this is a response to substrate stiffness. Hyperhydrated collagen gels were plastic-compressed (PC) to give a predetermined collagen density and stiffness. Mechanical properties were tested using a dynamic mechanical analyser; cell number by Alamar blue assay. In the stiffest PC matrices, cell proliferation was rapid and seeding density-dependent, with a population doubling time of 2 days. In contrast, compliant attached matrices showed a 4 day lag period and a doubling time of 6 days. HDF growth was directly related to matrix stiffness, such that increasing stiffness using a range of compression levels (0,75% fluid removal) supported increasing proliferation rate, doubling times and matrix elastic modulus. HDF quiescence in compliant matrices was reversible, such that increasing stiffness in situ by compression at 1 and 5 days initiated proliferation. We conclude that collagen matrix stiffness regulates proliferation of fibroblasts (a duro-response), with important implications for understanding fibroblast,matrix feedback controls during wound healing and the design and regulation of engineered connective tissues based on collagen and other hydrogel-based scaffolds. Copyright © 2008 John Wiley & Sons, Ltd. [source] A critical review of the pharmacology of the plant extract of Pygeum africanum in the treatment of LUTS,NEUROUROLOGY AND URODYNAMICS, Issue 4 2007Alan D. Edgar Abstract Despite an unremitting increase in the number of patients presenting symptoms of benign prostate hyperplasia (BPH), the viable treatment options remain relatively limited when compared to other disorders of aging. This has spurred an interest in so-called alternative medicines, many of which continue to be used in spite of the more recent emergence of rationally targeted therapies. Nonetheless, in the case of plant extracts, the vast majority of these have not been subjected to the same rigorous pre-clinical pharmacological testing and large-scale clinical trials now required by health authorities. Furthermore, demonstration of their clinical efficacy in BPH has been hindered by trials of limited duration with a high placebo response. Beginning with a preliminary demonstration of in vitro inhibition of growth factor-mediated fibroblast proliferation with Pygeum africanum extract, a detailed series of in vitro and in vivo studies on prostate growth and bladder function were undertaken. These studies, reviewed herein, have permitted the identification of putative molecular targets of Pygeum africanum extract affecting both growth factor-mediated prostate growth as well as specific parameters of bladder function. These results, corroborated in part by short-term clinical efficacy, set the stage for a large-scale clinical trial to investigate the efficacy of Pygeum africanum extract in the treatment of lower urinary tract symptoms. Neurourol. Urodynam. 26:458,463, 2007. © 2007 Wiley-Liss, Inc. [source] Successful Treatment of Laryngeal Stenosis in Laryngo-Onycho-Cutaneous Syndrome with Topical Mitomycin CPEDIATRIC DERMATOLOGY, Issue 1 2006M.R.C.S., P. Seamus Phillips B.M. It affects the skin, nails, and larynx. Laryngeal involvement may cause lethal airway obstruction, and has in the past proved very difficult to treat. Mitomycin C is an antibiotic that acts as an alkylating agent, inhibiting DNA synthesis. It reduces fibroblast proliferation, and has previously been used to treat choanal atresia and laryngeal stenosis. We report an 18-year-old man with complete transglottic laryngeal stenosis secondary to laryngo-onycho-cutaneous syndrome. An airway was established by dissection with a bougie and sickle knife, and was initially maintained by the upper limb of a Montgomery T-tube. Laryngeal granulation tissue present on removal of the T-tube was treated with topical mitomycin C (2 mg/mL) applied for 4 minutes on two occasions with an interval of 1 month. A year later, the airway remained patent, with no granulation tissue. [source] Effects of Mitomycin-C on Normal Dermal Fibroblasts,THE LARYNGOSCOPE, Issue 4 2006Theodore Chen MD Abstract Objectives: To evaluate the effects of mitomycin-C on the growth and autocrine growth factor production of human dermal fibroblasts from the face. Study Design: In vitro study using normal adult dermal fibroblast cell lines in a serum-free model. Methods: Cell cultures were exposed to 4 mg/mL, 0.4 mg/mL, 0.04 mg/mL, 0.004 mg/mL, and 0.0004 mg/mL concentrations of mitomycin-C solution. Cell counts were performed, and the cell-free supernatants were collected at 0, 1, 3, and 5 days after the initial exposure. Population doubling times were calculated and supernatants were quantitatively assayed for basic fibroblast growth factor (bFGF) and transforming growth factor (TGF)-,1. Results: Continuous exposure to mitomycin-C caused fibroblast cell death by day 7 at all tested concentrations. A 4 minute exposure to mitomycin-C at 4 mg/mL caused rapid fibroblast cell death. A 4-minute exposure to mitomycin-C at either 0.4 mg/mL or 0.04 mg/mL resulted in decreased fibroblast proliferation. A 4 minute exposure to mitomycin-C at 0.4 mg/mL resulted in a marked increase in the production of both bFGF and TGF-,1. Conclusions: A clinically ideal concentration of mitomycin-C would slow fibroblast proliferation yet not cause cell death to allow for a wound healing response. Mitomycin-C 0.4 mg/mL for 4 minutes satisfies the above criteria in vitro. [source] Dabigatran, a direct thrombin inhibitor, demonstrates antifibrotic effects on lung fibroblastsARTHRITIS & RHEUMATISM, Issue 11 2009Galina S. Bogatkevich Objective Myofibroblasts are the principal mesenchymal cells responsible for tissue remodeling, collagen deposition, and the restrictive nature of lung parenchyma associated with pulmonary fibrosis. We previously reported that thrombin activates protease-activated receptor 1 (PAR-1) and induces a myofibroblast phenotype in normal lung fibroblasts resembling the phenotype of scleroderma lung myofibroblasts. We undertook this study to investigate whether a selective direct thrombin inhibitor, dabigatran, interferes with signal transduction in human lung fibroblasts induced by thrombin and mediated via PAR-1. Methods Lung fibroblast proliferation was analyzed using the Quick Cell Proliferation Assay. Expression and organization of ,-smooth muscle actin (,-SMA) was studied by immunofluorescence staining and immunoblotting. Contractile activity of lung fibroblasts was measured by a collagen gel contraction assay. Connective tissue growth factor (CTGF) and type I collagen expression was analyzed on Western blots. Results Dabigatran, at concentrations of 50,1,000 ng/ml, inhibited thrombin-induced cell proliferation, ,-SMA expression and organization, and the production of collagen and CTGF in normal lung fibroblasts. Moreover, when treated with dabigatran (1 ,g/ml), scleroderma lung myofibroblasts produced 6-fold less ,-SMA, 3-fold less CTGF, and 2-fold less type I collagen compared with untreated cells. Conclusion Dabigatran restrains important profibrotic events in lung fibroblasts and warrants study as a potential antifibrotic drug for the treatment of fibrosing lung diseases such as scleroderma lung disease and idiopathic pulmonary fibrosis. [source] Attenuation of Bleomycin-Induced Lung Fibrosis by Oxymatrine Is Associated with Regulation of Fibroblast Proliferation and Collagen Production in Primary CultureBASIC AND CLINICAL PHARMACOLOGY & TOXICOLOGY, Issue 3 2008Xiaohong Chen Oxymatrine is an alkaloid extracted from the Chinese herb Sophora japonica (Sophora flavescens Ait.) with capacities of anti-inflammation, inhibition of immune reaction, antivirus, protection against acute lung injury and antihepatic fibrosis. In this study, the effect of oxymatrine on pulmonary fibrosis was investigated using a bleomycin-induced pulmonary fibrosis mouse model. The results showed that bleomycin challenge provoked severe pulmonary fibrosis with marked increase in hydroxyproline content of lung tissue and lung fibrosis fraction, which was prevented by oxymatrine in a dose-dependent manner. In addition, bleomycin injection resulted in a marked increase of myeloperoxidase activity and malondialdehyde level that was attenuated by oxymatrine. Administration of oxymatrine inhibited the proliferation of murine lung fibroblasts, arrested the cells at G0/G1 phase and reduced the expression of cell cycle regulatory protein, cyclin D1 in vitro. Furthermore, the steady-state production of collagen and the expression of ,1(I) pro-collagen and ,2(I) pro-collagen mRNA in fibroblasts were inhibited by oxymatrine in a dose-dependent manner. These results suggested that oxymatrine may attenuate pulmonary fibrosis induced by bleomycin in mice, partly through inhibition of inflammatory response and lipid peroxidation in lung induced by bleomycin and reduction of fibroblast proliferation and collagen synthesis. [source] Dermal fibroblast-associated gene induction by asiaticoside shown in vitro by DNA microarray analysisBRITISH JOURNAL OF DERMATOLOGY, Issue 3 2004L. Lu Summary Background, Asiaticoside, isolated from Centella asiatica, promotes fibroblast proliferation and extracellular matrix (ECM) synthesis in wound healing. The precise mechanism, however, in molecular and gene expression levels is still unclear. Objective, Using cDNA microarray technology, the alteration of gene expression profiles was determined for human dermal fibroblasts in vitro in the presence of asiaticoside (30 ,g mL,1). Fifty-four genes, with known functions for cell proliferation, cell cycle progression and synthesis of ECM, were significantly upregulated in our ,genome-nest' expression profile at various time points. Furthermore, the mRNA levels and protein production of certain genes responsible for ECM synthesis (e.g. encoding type I and type III collagen proteins) were evaluated by Northern blot and radioimmunoassay, respectively. Results, We found that there is a close correlation between the gene profile, mRNA and protein production in the response of the cells to asiaticoside stimulation. Conclusions, This information could be used for exploring the response of the target genes to asiaticoside in fibroblasts. [source] Expression and regulation of connective tissue growth factor by transforming growth factor , and tumour necrosis factor , in fibroblasts isolated from strictures in patients with Crohn's diseaseBRITISH JOURNAL OF SURGERY (NOW INCLUDES EUROPEAN JOURNAL OF SURGERY), Issue 10 2006D. Beddy Background: Connective tissue growth factor (CTGF) stimulates fibroblast proliferation and extracellular matrix production. Fibroblasts may initiate stricture formation in Crohn's disease through overexpression of CTGF. Stricturing that occurs in patients with Crohn's disease after treatment with anti-tumour necrosis factor (TNF) , may be due to dysregulation of CTGF homeostasis. The aim of this study was to examine CTGF expression and regulation in fibroblasts isolated from patients with Crohn's disease. Methods: Fibroblasts were isolated by a primary explant technique from serosal biopsies of strictured segments of bowel in eight patients undergoing resection for Crohn's disease and from normal colon in seven patients having resection for benign or malignant colorectal disease. Cells were stimulated with transforming growth factor (TGF) , and TNF-,. CTGF protein and mRNA expression were measured by western blotting and real-time polymerase chain reaction respectively. Results: Mean(s.d.) CTGF protein expression in strictured Crohn's fibroblasts was higher than that in normal fibroblasts (56·5(9·7) versus 17·0(10·0) respectively; P = 0·011). In normal and strictured Crohn's fibroblasts, culture with TGF-, increased CTGF protein and mRNA expression. Co-culture of normal fibroblasts with TNF-, suppressed TGF-,-stimulated CTGF expression. Conclusion: Increased expression of CTGF in strictured Crohn's fibroblasts underlies its role in fibrosis. TNF-, suppresses fibrosis by downregulating fibroblast CTGF expression, an effect that may be lost following anti-TNF-, treatment, thereby promoting stricture formation. Copyright © 2006 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd. [source] A novel type II membrane receptor up-regulated by IFN-, in fibroblasts functions in cell proliferation through the JAK-STAT signalling pathwayCELL PROLIFERATION, Issue 2 2006L.-D. Liu Structural analysis and immunofluorescence detection has suggested that this protein is located on the surface of fibroblasts, generally considered, a receptor. Cell proliferation assay has revealed that activation of TIIMPSC elevates the level of fibroblast proliferation. Further, examination of signal transduction has indicated that expression of this protein is up-regulated by IFN-, stimulation, and that it is involved in the regulation of fibroblast growth through the JAK-STAT signalling pathway. [source] Airway epithelium-derived transforming growth factor-, is a regulator of fibroblast proliferation in both fibrotic and normal subjectsCLINICAL & EXPERIMENTAL ALLERGY, Issue 8 2008K. E. Hostettler Summary Background In the healthy lung, airway epithelial cells (AEC) regulate fibroblast proliferation through release of soluble factors, such as prostaglandins and proteins. Fibroproliferative diseases and airway remodelling may result from an inadequate generation of suppressive factors by AEC or the inability of fibroblasts to respond to them appropriately. Objective The aim of this study was to study the effect of primary human AEC on the proliferation of fibroblasts obtained from healthy and fibrotic lungs in an interactive cell culture model. Results Conditioned medium (CM) from 14 out of 16 AEC lines significantly inhibited proliferation of normal human lung fibroblasts by 51.2±6.0%. The proliferation of fibroblasts derived from patients with lung fibrosis was equally inhibited by CM of AEC. The inhibitory effect of AEC-CM was completely reversed when fibroblasts were pre-incubated with 2.5 ,m indomethacin. Furthermore, primary human AEC, but not fibroblasts, secrete TGF-,, and the inhibitory effect of the AEC-CM was blocked by neutralizing anti-TGF-, antibodies. Conclusion These results demonstrate that AEC actively inhibit the proliferation of both normal and fibrotic fibroblasts via TGF-,, which induces the prostaglandin E2 synthesis in fibroblasts. The data indicate that proliferative lung diseases may be treated using the epithelial cell as the target of medication. [source] | ||||||||||||||||||||||||||||