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Collagen Degradation (collagen + degradation)
Selected AbstractsDifferential Long-Term Stimulation of Type I versus Type III Collagen After Infrared IrradiationDERMATOLOGIC SURGERY, Issue 7 2009YOHEI TANAKA MD BACKGROUND The dermis is composed primarily of type I (soft) and type III (rigid scar-like) collagen. Collagen degradation is considered the primary cause of skin aging. Studies have proved the efficacy of infrared irradiation on collagen stimulation but have not investigated the differential long-term effects of infrared irradiation on type I and type III collagen. OBJECTIVE To determine differential long-term stimulation of type I and type III collagen after infrared (1,100,1,800 nm) irradiation. METHODS AND MATERIALS In vivo rat tissue was irradiated using the infrared device. Histology samples were analyzed for type I and III collagen stimulation, visual changes from baseline, and treatment safety up to 90 days post-treatment. RESULTS Infrared irradiation provided long-term stimulation of type I collagen and temporary stimulation of type III collagen. Treatment also created long-term smoothing of the epidermis, with no observed complications. CONCLUSIONS Infrared irradiation provides safe, consistent, long-term stimulation of type I collagen but only short-term stimulation in the more rigid type III collagen. This is preferential for cosmetic patients looking for improvement in laxity and wrinkles while seeking smoother, more youthful skin. [source] Adenosine reverses a preestablished CCl4 -induced micronodular cirrhosis through enhancing collagenolytic activity and stimulating hepatocyte cell proliferation in ratsHEPATOLOGY, Issue 4 2001Rolando Hernández-Muñoz Cirrhosis is one of the most common causes of mortality worldwide, because hepatic dysfunction constitutes a potentially lethal condition. Having demonstrated the hepatoprotective effect of adenosine against CCl4 -induced cirrhosis, the present study was aimed at assessing adenosine's effect on an already-established micronodular cirrhosis. Chronic administration of CCl4 (10 weeks) induced a cirrhotic state, characterized by increased liver fibronectin and collagen types I and III content, enhanced expression of ,-1 (I) collagen mRNA, portal hypertension, and liver dysfunction. After CCl4 discontinuation (5 weeks), increased persitance of ,-1 (I) collagen mRNA expression and deposition, enhanced proline incorporation into collagen and prolyl hydroxylase activity evidenced active fibrogenesis. Several weeks after CCl4 withdrawal, deposited collagen showed an enhanced type I/III ratio, which was associated with deficient collagenolytic activity in cirrhotic livers. Liver expression of some metalloproteinases (MMPs) and of tissue inhibitors of MMPs (TIMPs) also indicated decreased collagen breakdown in cirrhotic livers. Parameters indicative of oxidative stress (mainly protein oxidation) were persistently augmented. These events were coincident with diminished regenerative capacity of the cirrhotic liver. Intraperitoneal adenosine administration to CCl4 -induced cirrhotic rats blocked active fibrogenesis and increased the collagen degradation (most probably by decreasing liver TIMPs levels), normalizing collagen-type ratios. In addition, the nucleoside promoted an effective hepatocyte's proliferation in the cirrhotic liver and accelerated normalization of parameters indicative of liver function and oxidative stress. Thus, adenosine readily reversed an experimental cirrhosis through stimulating liver collagenolytic and proliferative capacities, as well as by accelerating functional recovery. [source] Treatment of chronic liver diseases with traditional Chinese medicineJOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 2000Bao-En Wang Traditional Chinese medicine is still being extensively used for treatment of liver disease in China. The anti-viral herbs, Phyllanthus amarus, P. niruri and P. urninaria, and Oxymatrine extracted from Sophora flavecientis and S. subprostratae, have been shown to have a remarkable HBV suppressing effect with a serum conversion rate for HBeAg and HBV DNA around 45%, similar to that of IFN-,. The anti-inflammatory compound, Stronger NeoMinophagen C (SNMC), is a Japanese preparation of glycerrhizin, extracted from Glyceriza glabra, which has shown an effective rate of ALT and AST normalization and reduction to < 60 U/L in 65.6% and 73.5% of patients. Compound 861, made of 10 herbs with Salvia miltiorrhiza as its chief component, has been shown experimentally to be effective in suppressing fibrogenesis, enhancing collagen degradation, and inhibiting TIMP expression. Clinically, an open trial of 2000 patients showed improvement of symptoms in 83% and normalization of serum ALT in 82%. In a controlled study of 107 patients with HBV-related diseases, double liver biopsies showed that the fibrosis reversal rate after 6 months treatment with Cpd 861 was 78% in S2, 82% in S3 (precirrhotic stage) and 75% in S4 (early cirrhosis), as assessed by Scheuer's and Chevallier's criterion. In conclusion, traditional Chinese medicine has great potential in the treatment of chronic hepatitis B. [source] Platelet-rich plasma impairs osteoclast generation from human precursors of peripheral bloodJOURNAL OF ORTHOPAEDIC RESEARCH, Issue 6 2010Elisabetta Cenni Abstract Platelet-rich plasma is used to accelerate bone repair for the release of osteogenic growth factors from activated platelets. To date, the effects on osteoclasts have been only scarcely investigated, even though these cells are crucial for bone remodeling. The aim of this research was the evaluation of the effects of thrombin-activated platelets (PRP) on osteoclastogenesis from human blood precursors. We evaluated both the ability to influence osteoclast differentiation induced by the receptor activator of nuclear factor-kappaB ligand (RANKL), and the ability to induce osteoclast differentiation without RANKL. In both assays, the incubation with PRP supernatant at 10% did not significantly affect the formation of tartrate-resistant acid phosphatase (TRACP)-positive multinucleated cells that were able to form the F-actin ring. However, when PRP at 25 and 50% was added to the medium without RANKL, the generation of TRACP-positive multinucleated cells was inhibited. PRP, even at 10%, reduced the osteoclast-mediated bone collagen degradation, suggesting inhibition of osteoclast activation. Similarly, after incubation with PRP supernatant, calcitonin receptor mRNA was lower than the untreated samples. In conclusion, PRP at 10% interfered with the complete differentiation process of human osteoclast precursors. At higher concentration it impaired osteoclast formation also at an early stage of differentiation. © 2010 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 28:792,797, 2010 [source] Low-intensity pulsed ultrasound (LIPUS) increases the articular cartilage type II collagen in a rat osteoarthritis modelJOURNAL OF ORTHOPAEDIC RESEARCH, Issue 3 2010Kiyohito Naito Abstract In this study, the effect of low-intensity pulsed ultrasound (LIPUS) on cartilage was evaluated in a rat osteoarthritis (OA) model using serum biomarkers such as CTX-II (type II collagen degradation) and CPII (type II collagen synthesis) as well as histological criteria (Mankin score and immunohistochemical type II collagen staining). OA was surgically induced in the knee joint of rats by anterior cruciate/medial collateral ligament transection and medial meniscus resection (ACLT,+,MMx). Animals were divided into three groups: sham-operated group (Sham), ACLT,+,MMx group without LIPUS (,LIPUS), and ACLT,+,MMx group with LIPUS (+LIPUS; 30 mW/cm2, 20 min/day for 28 days). CTX-II levels were elevated in both ,LIPUS and +LIPUS groups compared to that in the Sham group after the operation, but there was no significant difference between +LIPUS and ,LIPUS groups, suggesting that LIPUS does not affect the degradation of type II collagen in this model. In contrast, CPII was significantly increased in +LIPUS group compared to ,LIPUS and Sham. Moreover, histological damage on the cartilage (Mankin score) was ameliorated by LIPUS, and type II collagen was immunohistochemically increased by LIPUS in the cartilage of an OA model. Of interest, mRNA expression of type II collagen was enhanced by LIPUS in chondrocytes. Together these observations suggest that LIPUS is likely to increase the type II collagen synthesis in articular cartilage, possibly via the activation of chondrocytes and induction of type II collagen mRNA expression, thereby exhibiting chondroprotective action in a rat OA model. © 2009 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 28:361,369, 2010 [source] MMP-mediated collagen breakdown induced by activated protein C in equine cartilage is reduced by corticosteroidsJOURNAL OF ORTHOPAEDIC RESEARCH, Issue 3 2010Elaine R. Garvican Abstract The plasma serine protease activated protein C (APC) is synthesized by human chondrocytes at sites of pathological cartilage fibrillation. APC levels are increased in osteoarthritis (OA) synovial fluid, and in vitro APC has been shown to synergize with interleukin-1, (IL-1) to promote degradation from ovine cartilage. A model of equine cartilage degradation was established and used to explore corticosteroid activities. Intraarticular corticosteroids are a commonly prescribed treatment for joint disease, however their role in disease modification remains unclear. APC synergized with IL-1 or tumor necrosis factor-, (TNF,), promoting significant collagen degradation from equine cartilage explants within 4 days, but did not augment glycoaminoglycan (GAG) release. APC activated pro-matrix metalloproteinases (MMP)-2 but not pro-MMP-9, as assessed by gelatin zymography. APC did not directly activate pro-MMP-13. Dexamethasone, triamcinolone, and methylprednisolone acetate (MPA) were evaluated at concentrations between 10, 5M and 10,10M. High concentrations significantly increased GAG release from IL-1+APC,treated explants. With the exception of MPA at 10,10M, all concentrations of corticosteroids caused significant decreases in IL-1+APC-driven hydroxyproline loss. Treatment with corticosteroids suppressed expression of MMP-1, -3, and -13 mRNA. The collagenolysis associated with IL-1+APC synergy, and the inhibition of this effect by corticosteroids may involve gelatinase activation and downregulation of MMP expression, respectively. © 2009 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 28:370,378, 2010 [source] Continuous supply of TGF,3 via adenoviral vector promotes type I collagen and viability of fibroblasts in alginate hydrogelJOURNAL OF TISSUE ENGINEERING AND REGENERATIVE MEDICINE, Issue 7 2010Yongchang Yao Abstract In recent years, transforming growth factor-,3 (TGF,3) has interested more and more researchers with its competence in engineered histogenesis. In the present study we employed recombinant adenoviral vectors to deliver the constitutively active TGF,3 gene to human dermal fibroblasts, which could maintain the continuous secretion of TGF,3 from the cells. The expression of type I collagen in the Ad-TGF,3 group increased significantly in comparison with other three groups: Neg (cells without treatment of the adenovirus), Ad-null (cells with treatment of the adenovirus, without the inserted gene) and Ad-shRNA (cells with treatment of the adenovirus encoding shRNA specific for type I collagen). Additionally, we demonstrated that TGF,3 enhanced the expression of Smad4 while inhibiting that of MMP-9, thus promoting the collagen transcription via the Smad signal transduction pathway and restraining collagen degradation by MMP-9, which contributed to the increasing type I collagen expression level. As type I collagen mediates cell,material interactions by providing anchorage, the viability of encapsulated fibroblasts in Ad-TGF,3 group was significantly higher than that in other three groups. Accordingly, this approach forms an effective way to improve the compatibility of non-adhesive hydrogels containing anchorage-dependent cells. Copyright © 2010 John Wiley & Sons, Ltd. [source] Anti-wrinkling effects of the mixture of vitamin C, vitamin E, pycnogenol and evening primrose oil, and molecular mechanisms on hairless mouse skin caused by chronic ultraviolet B irradiationPHOTODERMATOLOGY, PHOTOIMMUNOLOGY & PHOTOMEDICINE, Issue 5 2007Ho-Song Cho Background: Naturally occurring antioxidants were used to regulate the skin damage caused by ultraviolet (UV) radiation because several antioxidants have demonstrated that they can inhibit wrinkle formation through prevention of matrix metalloproteinases (MMPs) and/or increase of collagen synthesis. Objective: We examined the effect of oral administration of the antioxidant mixture of vitamin C, vitamin E, pycnogenol, and evening primrose oil on UVB-induced wrinkle formation. In addition, we investigated the possible molecular mechanism of photoprotection against UVB through inhibition of collagen-degrading MMP activity or through enhancement of procollagen synthesis in mouse dorsal skin. Methods: Female SKH-1 hairless mice were orally administrated the antioxidant mixture (test group) or vehicle (control group) for 10 weeks with UVB irradiation three times a week. The intensity of irradiation was gradually increased from 30 to 180 mJ/cm2. Microtopographic and histological assessment of the dorsal skins was carried out at the end of 10 weeks to evaluate wrinkle formation. Western blot analysis and EMSA were also carried out to investigate the changes in the balance of collagen synthesis and collagen degradation. Results: Our antioxidant mixture significantly reduced UVB-induced wrinkle formation, accompanied by significant reduction of epidermal thickness, and UVB-induced hyperplasia, acanthosis, and hyperkeratosis. This antioxidant mixture significantly prevented the UVB-induced expressions of MMPs, mitogen-activated protein (MAP) kinase, and activation of activator protein (AP)-1 transcriptional factor in addition to enhanced type I procollagen and transforming growth factor-,2 (TGF-,2) expression. Conclusion: Oral administration of the antioxidant mixture significantly inhibited wrinkle formation caused by chronic UVB irradiation through significant inhibition of UVB-induced MMP activity accompanied by enhancement of collagen synthesis. [source] The S2 subsites of cathepsins K and L and their contribution to collagen degradationPROTEIN SCIENCE, Issue 4 2007Fabien Lecaille Abstract The exchange of residues 67 and 205 of the S2 pocket of human cysteine cathepsins K and L induces a permutation of their substrate specificity toward fluorogenic peptide substrates. While the cathepsin L-like cathepsin K (Tyr67Leu/Leu205Ala) mutant has a marked preference for Phe, the Leu67Tyr/Ala205Leu cathepsin L variant shows an effective cathepsin K-like preference for Leu and Pro. A similar turnaround of inhibition was observed by using specific inhibitors of cathepsin K [1-(N -Benzyloxycarbonyl-leucyl)-5-(N -Boc-phenylalanyl-leucyl)carbohydrazide] and cathepsin L [N -(4-biphenylacetyl)- S -methylcysteine-(D)-Arg-Phe-,-phenethylamide]. Molecular modeling studies indicated that mutations alter the character of both S2 and S3 subsites, while docking calculations were consistent with kinetics data. The cathepsin K-like cathepsin L was unable to mimic the collagen-degrading activity of cathepsin K against collagens I and II, DQ-collagens I and IV, and elastin-Congo Red. In summary, double mutations of the S2 pocket of cathepsins K (Y67L/L205A) and L (L67Y/A205L) induce a switch of their enzymatic specificity toward small selective inhibitors and peptidyl substrates, confirming the key role of residues 67 and 205. However, mutations in the S2 subsite pocket of cathepsin L alone without engineering of binding sites to chondroitin sulfate are not sufficient to generate a cathepsin K-like collagenase, emphasizing the pivotal role of the complex formation between glycosaminoglycans and cathepsin K for its unique collagenolytic activity. [source] Ultrastructural changes induced in cutaneous collagen by ultraviolet-A1 and psoralen plus ultraviolet A therapy in systemic sclerosisTHE JOURNAL OF DERMATOLOGY, Issue 2 2008Noriyuki SAKAKIBARA ABSTRACT In the present study, we examined the ultrastructural alterations in collagen fibrils clinically softened by ultraviolet-A1 (UVA1, 340,400 nm) therapy and psoralen plus long-wave ultraviolet (PUVA) therapy and compared collagen fibril diameters in four patients with systemic sclerosis (SSc). In skin sclerosis, the dermis is compacted from the epidermal layer to the sweat glands, and the collagen bundles are thicker with decreased space between them. We obtained skin specimens before and after UVA1 or PUVA therapy, and compared cutaneous alterations in one diffuse-type patient and one limited-type patient following UVA1 therapy, and in two diffuse-type patients following PUVA treatment. Ultramicroscopic analysis revealed that UVA1 treatment decreased the diameter of the broad collagen fibrils, mainly in the upper reticular layer. PUVA induced similar alterations in the collagen fibrils, extending to the upper and middle reticular layers. PUVA therapy induced alterations in collagen fibril diameter in deeper layers than did UVA1 therapy, which might be related to the direct action of UV light and the depth of the light penetration. In three of four patients, collagen fibril diameter decreased, collagen fibril thickness equalized, and new, thin fibrils developed among the collagen fibrils, suggesting that collagen degradation and synthesis underlie the alterations induced by UVA1 and PUVA phototherapies. [source] Prevention of cartilage degeneration and restoration of chondroprotection by lubricin tribosupplementation in the rat following anterior cruciate ligament transectionARTHRITIS & RHEUMATISM, Issue 8 2010Gregory D. Jay Objective To investigate whether cartilage degeneration is prevented or minimized following intraarticular injections of lubricin derived from human synoviocytes in culture, recombinant human PRG4 (rhPRG4), or human synovial fluid (SF) in a rat model of anterior cruciate ligament (ACL) injury. Methods Unilateral ACL transection (ACLT) was performed in Lewis rats (n = 45). Nine animals were left untreated. The remaining rats were given intraarticular injections (50 ,l/injection) of either phosphate buffered saline (PBS) (n = 9), human synoviocyte lubricin (200 ,g/ml; n = 9), rhPRG4 (200 ,g/ml; n = 9), or human SF lubricin (200 ,g/ml; n = 9) twice weekly beginning on day 7 after injury. Joints were harvested on day 32 after injury. Histologic analysis was performed using Safranin O,fast green staining, and articular cartilage degeneration was graded using the Osteoarthritis Research Society International (OARSI),modified Mankin criteria. Histologic specimens were immunoprobed for lubricin and sulfated glycosaminoglycans. A 24-hour urine collection was performed on days 17 and 29 postinjury, and urinary C-terminal telopeptide of type II collagen (CTX-II) levels were measured. Results Treatment with human synoviocyte lubricin resulted in significantly lower OARSI scores for cartilage degeneration compared with no treatment or PBS treatment (P < 0.05). Increased immunostaining for lubricin in the superficial zone chondrocytes and on the surface of cartilage was observed in lubricin-treated, but not untreated or PBS-treated, joints. On day 17, urinary CTX-II levels in human synoviocyte lubricin, and human SF lubricin,treated animals were significantly lower than those in untreated animals (P = 0.005 and P = 0.002, respectively) and in PBS-treated animals (P = 0.002 and P < 0.001, respectively). Conclusion After treatment with any of the 3 types of lubricin evaluated in this study, a reduction in cartilage damage following ACLT was evident, combined with a reduction in type II collagen degradation. Our findings indicate that intraarticular lubricin injection following an ACL injury may be beneficial in retarding the degeneration of cartilage and the development of posttraumatic OA. [source] Activation of cartilage matrix metalloproteinases by activated protein CARTHRITIS & RHEUMATISM, Issue 3 2009Miriam T. Jackson Objective To investigate the role of activated protein C (APC) in cartilage degradation. Methods Chondrocyte expression of protein C, endothelial protein C receptor (EPCR), and thrombomodulin (TM) were evaluated by reverse transcription,polymerase chain reaction (RT-PCR). APC was immunolocalized in developing joints and in osteoarthritic (OA) cartilage from humans. The effect of APC on aggrecan and collagen degradation was examined in explant cultures of ovine cartilage in control cultures and in cultures stimulated with interleukin-1, (IL-1,), tumor necrosis factor , (TNF,), or retinoic acid (RetA), using colorimetric assays and Western blotting. Chondrocyte expression of matrix metalloproteinases (MMPs), ADAMTS, and tissue inhibitor of metalloproteinases (TIMPs) was measured by RT-PCR. MMP-2 and MMP-9 activity was evaluated by gelatin zymography and MMP-13 by fluorogenic assay. Results Positive cellular immunostaining for APC was found at sites of MMP activity in developing joints and in OA, but not normal, cartilage. Chondrocytes expressed messenger RNA for protein C, EPCR, and TM, with the latter 2 levels increased by IL-1, and TNF, stimulation. APC augmented aggrecan release and initiated collagen breakdown in IL-1,,treated and TNF,-treated cartilage, but not in normal or in RetA-treated cartilage. APC-stimulated aggrecan and collagen breakdown were due to MMP activity but were not associated with modulation of MMP, ADAMTS, or TIMP expression. APC resulted in MMP-13 activation in cartilage cultures. APC could not directly activate proMMP-13, but it was associated with increased MMP-2 and MMP-9 activity. Conclusion APC may be a relevant activator of MMPs in cartilage and may play a role in progressive cartilage degradation in arthritis. [source] The chemical biomarkers C2C, Coll2-1, and Coll2-1NO2 provide complementary information on type II collagen catabolism in healthy and osteoarthritic miceARTHRITIS & RHEUMATISM, Issue 10 2007L. G. Ameye Objective Compared with wild-type (WT) mice, biglycan/fibromodulin double-deficient mice develop severe knee osteoarthritis. We undertook this study to compare type II collagen catabolism in the 2 genotypes and to compare the usefulness of 3 biomarkers of collagen degradation (C2C [also known as Col2-3/4Clong mono] as well as the peptide Coll2-1 and its nitrated form, Coll2-1NO2) for evaluating collagen catabolism in vivo. Methods In 15 WT mice and 15 biglycan/fibromodulin double-deficient mice, we determined serum levels of C2C at ages 66 and 141 days, and we determined serum levels of Coll2-1 and Coll2-1NO2 at ages 49, 81, 95, and 141 days. Expression of the biomarkers in knee sections was examined using immunohistochemistry. Results The mean concentrations of C2C and Coll2-1 were higher in biglycan/fibromodulin double-deficient mice at all time points. For C2C and Coll2-1, the ratio of the serum concentration in biglycan/fibromodulin double-deficient mice to that in WT mice (the double-deficient:WT ratio) was constant over time and was ,1.63 and ,1.15, respectively. In contrast, the double-deficient:WT ratio for Coll2-1NO2 varied and, depending on age, was >1 or <1. No significant correlation was found between the expression of the different biomarkers, except for a weak, negative correlation between Coll2-1NO2 and C2C. In both genotypes, antibodies to each biomarker labeled some fibroblasts in the tendons and menisci as well as chondrocytes above the tidemark in articular cartilage. Growth plates were unstained. For each biomarker, extracellular staining was limited to fibrocartilage areas in the tendons and menisci in all mice and was limited to some focal lesions of the cartilage in biglycan/fibromodulin double-deficient mice. Conclusion The different double-deficient:WT ratios observed with C2C, Coll2-1, and Coll2-1NO2 in the absence of any correlation between the expression of the 3 biomarkers indicate that these biomarkers give complementary, rather than redundant, information about in vivo type II collagen catabolism. [source] Keloid-derived fibroblasts show increased secretion of factors involved in collagen turnover and depend on matrix metalloproteinase for migrationBRITISH JOURNAL OF DERMATOLOGY, Issue 2 2005M. Fujiwara Summary Background, ,A keloid is a specific skin lesion that expands beyond the boundaries of the original injury as it heals. Histologically, it is characterized by the excessive accumulation of collagen. However, the reasons for the expansion and the invasive nature of keloids remain unknown. Objectives, We evaluated collagen degradation and migration by cultured keloid fibroblasts based on the assumption that these variables were of functional relevance to the expanding and invasive nature of keloid lesions. Methods, Collagen production was investigated by the detection of type 1 collagen (procollagen type 1C peptide: P1P). Matrix metalloproteinase (MMP)-1 (interstitial collagenase) and MMP-2 (gelatinase-A), were investigated as elements of the collagen degradation system. Enzyme immunoassays were performed to measure the production of P1P, MMP-1, MMP-2, and tissue inhibitor of metalloproteinase (TIMP)-1. To assess the production of MMP-2 its gelatinolytic activity was measured by zymography using gelatin-containing gels. The participation of transforming growth factor-,1 (TGF-,1) in the production and degradation of collagen was also investigated. Finally, the migratory activity of keloid fibroblasts was evaluated using a colony dispersion assay. Results, The production of type 1 collagen, MMP-1, MMP-2, and TIMP-1 by keloid fibroblasts was 3-fold, 6-fold, 2·4-fold, and 2-fold greater than that of normal dermal fibroblasts, respectively. Production of P1P was increased when TGF-,1 was added to cultures of keloid fibroblasts, while it was decreased when anti-TGF-,1 antibody was added to the cultures. In contrast, the production of MMP-1 was decreased by the addition of TGF-,1 to cultured keloid fibroblasts, while it was increased when anti-TGF-,1 antibody was added to the cultures. The production of MMP-2 increased after treatment with TGF-,1, but did not change significantly when anti-TGF-,1 antibody was added to the cultures. Production of TIMP-1 did not change significantly when either TGF-,1 or anti-TGF-,1 antibody was added to the cultures. Keloid fibroblasts showed a 2·5-fold increase of migratory activity compared with normal dermal fibroblasts, while the migratory activity of these fibroblasts was reduced to the control level by treatment with a broad-spectrum MMP inhibitor (GM 6001). Conclusions, Cultured keloid fibroblasts showed increased production of collagen and MMPs, and TGF-,1 played a role in this regulation of production. In addition, increased production of MMPs had a role in the high migratory activity of cultured keloid fibroblasts. [source] Matrix metalloproteinase 8 (neutrophil collagenase) in the pathogenesis of abdominal aortic aneurysm,BRITISH JOURNAL OF SURGERY (NOW INCLUDES EUROPEAN JOURNAL OF SURGERY), Issue 7 2005W. R. W. Wilson Background: Loss of elastin is the initiating event in abdominal aortic aneurysm (AAA) formation, whereas loss of collagen is required for continued expansion. The elastolytic matrix metalloproteinases (MMPs) 2 and 9 are well described, but the source of excessive collagenolysis remains undefined. The aim of this study was to determine the expression of MMP-8, a potent type I collagenase, in normal aorta and AAA. Methods: Infrarenal aortic biopsies were taken from 40 AAA and ten age-matched normal aortas. The concentrations of MMP-8 protein and its inhibitors, tissue inhibitor of metalloproteinase (TIMP) 1 and TIMP-2, were quantified by enzyme-linked immunosorbent assay. Immunohistochemistry was used to localize MMP-8 expression. Results: MMP-8 concentrations were significantly raised in AAA compared with normal aorta (active MMP-8: 4·5 versus 0·5 ng per mg protein, P < 0·001; total MMP-8: 16·6 versus 2·8 ng per mg protein, P < 0·001). Levels of TIMP-1 and TIMP-2 were significantly lower in AAA than in normal aortic samples (TIMP-1: 142·2 versus 302·8 ng per mg protein; P = 0·010; TIMP-2: 9·2 versus 33·1 ng per mg protein, P < 0·001). Immunohistochemistry localized MMP-8 to mesenchymal cells within the adventitia of the aortic wall. Conclusion: The high concentration of MMP-8 in aortic aneurysms represents a potent pathway for collagen degradation, and hence aneurysm formation and expansion. Copyright © 2005 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd. [source] Increases in collagen type I synthesis in asthma: the role of eosinophils and transforming growth factor-b,CLINICAL & EXPERIMENTAL ALLERGY, Issue 6 2002A. Nomura Summary Background Collagen type I is one of the major deposits in thickening of the reticular basement membrane of asthma. Objective and Methods In this study, we assessed turnover of collagen type I in asthma by measuring procollagen type I C-terminal peptide (PICP) and collagen type I C-terminal telopeptide (ICTP) in induced sputum. Results PICP but not ICTP was found to be significantly higher in asthma subjects than in normal volunteers (P < 0.05). In asthma, PICP was inversely correlated with %FEV1.0 (r = ,0.539), and its levels significantly increased upon exacerbation (P < 0.05), indicating that collagen synthesis increases during asthma exacerbation. Additionally, PICP was found to significantly correlate with eosinophil counts in sputum (r = 0.539), indicating that eosinophils stimulate collagen turnover. Because eosinophils can produce TGF-,, a potent stimulator of collagen synthesis, we immunocytochemically examined TGF-,-positive cells in sputum. TGF-,-positive cells significantly correlated with eosinophil counts (r = 0.811) and PICP (r = 0.569), suggesting that TGF-, released from eosinophils is involved in collagen synthesis. Conclusions The results of the present study suggest that collagen synthesis is stimulated in asthmatic airways by eosinophils through TGF-,, while collagen degradation is not, and that PICP in sputum can act as a new marker for airway inflammation in asthma. [source] Effects of short-term dexamethasone treatment on collagen synthesis and degradation markers in preterm infants with developing lung diseaseACTA PAEDIATRICA, Issue 5 2003T Saarela Aim: To assess the effects of dexamethasone treatment on collagen turnover in preterm infants. Methods: The serum concentrations of the amino-terminal propeptide of type I and III procollagens (PINP and PIIINP), which reflect rates of type I and III collagen synthesis, respectively, and the carboxyterminal telopeptide of type I procollagen (ICTP), which reflects the rate of type I collagen degradation, were monitored in 13 preterm infants receiving dexamethasone and 13 matched control infants without glucocorticoid treatment for a total period of 12 mo. Dexamethasone was started at a median age of 12 d and continued at tapering doses for a median total duration of 10 d. Blood samples were taken immediately after birth, at 7, 14 and 28 d of age and at 2, 3, 6, 9 and 12 mo. The same markers were also measured just before the initiation of dexamethasone and on days 1, 3, and 7 of treatment. Results: A striking decrease in all of the markers was already observed in every case on day 1 of dexamethasone, the suppression being greatest on day 3 and still considerable on day 7. The percentages from the pretreatment levels recorded on days 1, 3 and 7 were: for PINP 51, 26 and 45%; for PIIINP 63, 44% and 52%; and for ICTP 64, 41 and 51%. A rebound rise in PINP levels was seen in dexamethasone-treated infants, the levels exceeding those of the controls at 3 and 6 mo of age. A similar phenomenon was noted concerning PIIINP at 3 mo. The levels settled down at 9 and 12 mo. Conclusion: Dexamethasone causes an immediate, inevitable, deep suppression of type I and III collagen synthesis and also type I collagen degradation. This should be taken into consideration, e.g. when assessing for the indications for steroid treatment in sick preterm infants and its dosing and duration. [source] | ||||||||||