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Extracellular Matrix Deposition (extracellular + matrix_deposition)

Distribution by Scientific Domains

Medical Sciences	76%
Life Sciences	23%

Selected Abstracts

Design of Fibrin Matrix Composition to Enhance Endothelial Cell Growth and Extracellular Matrix Deposition for In Vitro Tissue Engineering

ARTIFICIAL ORGANS, Issue 1 2009
Divya Pankajakshan
Abstract Tissue-engineered blood vessel substitutes should closely resemble native vessels in terms of structure, composition, mechanical properties, and function. Successful cardiovascular tissue engineering requires optimization of in vitro culture environment that would produce functional constructs. The extracellular matrix (ECM) protein elastin plays an essential role in the cardiovascular system to render elasticity to blood vessel wall, whereas collagen is responsible for providing mechanical strength. The objective of this study was to understand the significance of various ECM components on endothelial cell (EC) growth and tissue generation. We demonstrate that, even though fibrin is a good matrix for EC growth, fibronectin is the crucial component of the fibrin matrix that enhances EC adhesion, spreading, and proliferation. Vascular EC growth factor is known to influence in vitro growth of EC, but, so far, ECM deposition in in vitro culture has not been reported. In this study, it is shown that incorporation of a mixture of hypothalamus-derived angiogenic growth factors with fibrin matrix enhances synthesis and deposition of insoluble elastin and collagen in the matrix, within 10 days of in vitro culture. The results suggest that a carefully engineered fibrin composite matrix may support EC growth, survival, and remodeling of ECM in vitro and impart optimum properties to the construct for resisting the shear stress at the time of implantation. [source]

Effects of the combination of rapamycin with tacrolimus or cyclosporin on experimental intimal hyperplasia

BRITISH JOURNAL OF SURGERY (NOW INCLUDES EUROPEAN JOURNAL OF SURGERY), Issue 11 2002
Dr J. R. Waller
Background: Allograft vasculopathy remains the leading cause of late allograft failure following transplantation and can be inhibited by the antiproliferative drug rapamycin. This study assessed the efficacy of combining rapamycin therapy with calcineurin inhibition. Methods: Male Sprague,Dawley rats received rapamycin 0·05 mg/kg daily and either tacrolimus 0·1 mg/kg or cyclosporin 5 mg/kg daily, and findings were compared with those in an untreated control group. Animals underwent left common carotid artery balloon angioplasty; the artery was explanted after 2 weeks. Morphometric analysis was performed on transverse sections and the intima: media ratio was calculated. Profibrotic gene expression was measured with competitive reverse transcriptase,polymerase chain reaction at 14 and 28 days. Proliferation was determined with proliferating cell nuclear antigen at 14 and 28 days. Extracellular matrix deposition was quantified with Sirius red. Results: The combination of rapamycin and tacrolimus was associated with the greatest reduction in intimal thickening. Furthermore, treatment with rapamycin and tacrolimus significantly attenuated extracellular matrix deposition compared with rapamycin and cyclosporin (P < 0·02). Conclusion: The effects of rapamycin in combination with tacrolimus were better than those observed with rapamycin and cyclosporin. © 2002 British Journal of Surgery Society Ltd [source]

Protein kinase C and the development of diabetic vascular complications

DIABETIC MEDICINE, Issue 12 2001
K. J. Way
Abstract Hyperglycemic control in diabetes is key to preventing the development and progression of vascular complications such as retinopathy, nephropathy and neuropathy. Increased activation of the diacylglycerol (DAG)-protein kinase C (PKC) signal transduction pathway has been identified in vascular tissues from diabetic animals, and in vascular cells exposed to elevated glucose. Vascular abnormalities associated with glucose-induced PKC activation leading to increased synthesis of DAG include altered vascular blood flow, extracellular matrix deposition, basement membrane thickening, increased permeability and neovascularization. Preferential activation of the PKC, isoform by elevated glucose is reported to occur in a variety of vascular tissues. This has lead to the development of LY333531, a PKC, isoform specific inhibitor, which has shown potential in animal models to be an orally effective and nontoxic therapy able to produce significant improvements in diabetic retinopathy, nephropathy, neuropathy and cardiac dysfunction. Additionally, the antioxidant vitamin E has been identified as an inhibitor of the DAG-PKC pathway, and shows promise in reducing vascular complications in animal models of diabetes. Given the overwhelming evidence indicating a role for PKC activation in contributing to the development of diabetic vascular complications, pharmacological therapies that can modulate this pathway, particularly with PKC isoform selectivity, show great promise for treatment of vascular complications, even in the presence of hyperglycemia. Diabet. Med. 18, 945,959 (2001) [source]

Cellular and molecular mechanisms of bleomycin-induced murine scleroderma: current update and future perspective

EXPERIMENTAL DERMATOLOGY, Issue 2 2005
Toshiyuki Yamamoto
Abstract:, Scleroderma is a fibrotic condition characterized by immunologic abnormalities, vascular injury and increased accumulation of matrix proteins in the skin. Although the aetiology of scleroderma is not fully elucidated, a growing body of evidence suggests that extracellular matrix overproduction by activated fibroblasts results from complex interactions among endothelial cells, lymphocytes, macrophages and fibroblasts, via a number of mediators. Cytokines, chemokines and growth factors secreted by inflammatory cells and mesenchymal cells (fibroblasts and myofibroblasts) play an important role in the fibrotic process of scleroderma. Recently, we established a murine model of scleroderma by repeated local injections of bleomycin. Dermal sclerosis was induced in various mouse strains, although the intensity of dermal sclerosis varied among various strains. Histopathological and biochemical analysis demonstrated that this experimental murine scleroderma reflected a number of aspects of human scleroderma. Further investigation of the cellular and molecular mechanisms of inflammatory reaction, fibroblast activation and extracellular matrix deposition following dermal injury by bleomycin treatment will lead to the better understanding of the pathophysiology and the exploration of effective treatment against scleroderma. This review summarizes recent progress of the cellular and molecular events in the pathogenesis of bleomycin-induced scleroderma; moreover, further perspective by using this mouse model has been discussed. [source]

CCN2, connective tissue growth factor, stimulates collagen deposition by gingival fibroblasts via module 3 and ,6- and ,1 integrins

JOURNAL OF CELLULAR BIOCHEMISTRY, Issue 2 2006
Edwin C.K. Heng
Abstract CCN2, (connective tissue growth factor, CTGF) is a matricellular factor associated with fibrosis that plays an important role in the production and maintenance of fibrotic lesions. Increased collagen deposition and accumulation is a common feature of fibrotic tissues. The mechanisms by which CCN2/CTGF contributes to fibrosis are not well understood. Previous studies suggest that CTGF exerts some of its biological effects at least in part by integrin binding, though this mechanism has not been previously shown to contribute to fibrosis. Utilizing full length CCN2/CTGF, CCN2/CTGF fragments, and integrin neutralizing antibodies, we provide evidence that the effects of CCN2/CTGF to stimulate extracellular matrix deposition by gingival fibroblasts are mediated by the C-terminal half of CCN2/CTGF, and by ,6 and ,1 integrins. In addition, a synthetic peptide corresponding to a region of CCN2/CTGF domain 3 that binds ,6,1 inhibits the collagen-deposition assay. These studies employed a new and relatively rapid assay for CCN2/CTGF-stimulated collagen deposition based on Sirius Red staining of cell layers. Data obtained support a pathway in which CCN2/CTGF could bind to ,6,1 integrin and stimulate collagen deposition. These findings provide new experimental methodologies applicable to uncovering the mechanism and signal transduction pathways of CCN2/CTGF-mediated collagen deposition, and may provide insights into potential therapeutic strategies to treat gingival fibrosis and other fibrotic conditions. J. Cell. Biochem. 98: 409,420, 2006. © 2006 Wiley-Liss, Inc. [source]

Rosiglitazone treatment attenuates renal tissue inflammation generated by urinary tract obstruction

NEPHROLOGY, Issue 2 2009
SHAI EFRATI
SUMMARY Aim: Peroxisome proliferator-activated receptor (PPAR)-, activation by rosiglitazone decreases manifestation of intrarenal inflammatory hallmarks. Inflammation significantly aggravates renal injury following urinary tract obstruction. The effect of rosiglitazone on renal inflammation following unilateral ureteral obstruction was investigated. Methods: Ninety-six Srague,Dawley rats were subjected to unilateral ureteral ligation, or to sham operation. Half of each group received rosiglitazone, 5 mg/kg bodyweight per day. The animals were killed and their kidneys allocated following 1 h, 24 h or 2 weeks, for pathological examination or for intrarenal transforming growth factor (TGF)-,, interleukin (IL)-4, IL-6, IL-10 and nitric oxide (NO) assessment by specific enzyme-linked immunosorbent assays. Apoptosis rates, extracellular matrix deposition, PPAR-,, ,-smooth muscle actin (,-SMA) expression and macrophage infiltration were assessed by specific immunohistological stainings. Results: PPAR-, receptor expression was downregulated, and infiltration of macrophages decreased, in all rosiglitazone-treated kidneys. Rosiglitazone significantly decreased apoptosis, TGF-,, IL-6, ,-SMA expression and NO availability in obstructed kidneys. Synthesis of IL-10 was unaltered, while IL-4 augmented by Rosiglitazone. Rosiglitazone also affected NO and IL-4 production in sham-operated controls. Conclusion: (i) Rosiglitazone attenuates profibrotic and pro-inflammatory responses in a rat model of ureteral obstruction-induced renal inflammation; (ii) rosiglitazone stimulates counteractive anti-inflammatory responses in the damaged kidneys; (iii) in part, rosiglitazone exerts comparable anti-inflammatory effects on obstructed kidneys and unobstructed healthy controls. Taken together, this ascertains the importance of the anti-inflammatory role of rosiglitazone treatment in amelioration of ureteral obstruction-induced renal damage. [source]

Effect of Low Intensity Helium,Neon (HeNe) Laser Irradiation on Experimental Paracoccidioidomycotic Wound Healing Dynamics

PHOTOCHEMISTRY & PHOTOBIOLOGY, Issue 1 2009
Maria Carolina Ferreira
The effect of HeNe laser on the extracellular matrix deposition, chemokine expression and angiogenesis in experimental paracoccidioidomycotic lesions was investigated. At days 7, 8 and 9 postinfection the wound of each animal was treated with a 632.8 nm HeNe laser at a dose of 3 J cm,2. At day 10 postinfection, the wounds were examined by using histologic and immunohistochemical methods. Results revealed that laser-treated lesions were lesser extensive than untreated ones, and composed mainly by macrophages and lymphocytes. High IL-1, expression was shown in the untreated group whereas in laser-treated animals the expression was scarce. On the other hand, the expression of CXCL-10 was found to be reduced in untreated animals and quite intensive and well distributed in the laser-treated ones. Also, untreated lesions presented vascular endothelial growth factor (VEGF) in a small area near the center of the lesion and high immunoreactivity for hypoxia-inducible factor-1 (HIF-1), whereas laser-treated lesions expressed VEGF surrounding blood vessels and little immunoreactivity for HIF-1. Laser-treated lesions presented much more reticular fibers and collagen deposition when compared with the untreated lesion. Our results show that laser was efficient in minimizing the local effects observed in paracoccidioidomycosis and can be an efficient tool in the treatment of this infection, accelerating the healing process. [source]

Ganoderma lucidum extract attenuates the proliferation of hepatic stellate cells by blocking the PDGF receptor

PHYTOTHERAPY RESEARCH, Issue 6 2009
Guei-Jane Wang
Abstract Hepatic fibrosis is an outcome of chronic liver diseases. The activation and proliferation of hepatic stellate cells (HSCs) is a key event in liver injury. The fruiting body of Ganoderma lucidum has long been a popular oriental medicine for treating liver diseases. The aim of this present study was to investigate the antiproliferative effects of the triterpenoid-rich extract (GLT) of G. lucidum in a cell line of rat HSCs (HSC-T6) stimulated with platelet-derived growth factor (PDGF)-BB. DNA synthesis was investigated by bromodeoxyuridine (BrdU) incorporation. Flow cytometry using propidium iodide (PI) labeling was carried out to analyse the cell cycle distribution and apoptosis. , -Smooth muscle actin (, -SMA) was used to evaluate extracellular matrix deposition, and western blotting was performed to measure cyclins D1 and D2, and phosphorylation of the PDGF, -receptor (PDGF,R), Akt and JNK. The results indicated that the GLT attenuated BrdU incorporation in a concentration-dependent manner with an IC50 of 8.52 ± 0.33 µg/mL. The inhibitory effect of the GLT was associated with downregulation of cyclins D1 and D2, and PDGF,R and Akt phosphorylation, upregulation of JNK phosphorylation, and a reduction in , -SMA expression. These results indicated that G. lucidum inhibits PDGF-BB-activated HSC proliferation possibly through blocking PDGF,R phosphorylation, thereby indicating its efficacy for preventing and treating hepatic fibrosis. Copyright © 2008 John Wiley & Sons, Ltd. [source]

The urinary proteome in diabetes and diabetes-associated complications: New ways to assess disease progression and evaluate therapy

PROTEOMICS - CLINICAL APPLICATIONS, Issue 7-8 2008
Kasper Rossing
Abstract Diabetes represents one of the main chronic diseases worldwide. Diabetes and its associated complications may be detectable even at early stages in the urinary proteome. In this article we review the current literature on urinary proteomics applied to the study of diabetes and diabetic complications. Further, we present recent data that strongly indicate urinary proteome analysis may be a valuable tool in detecting diabetes-associated pathophysiological changes at an early stage, and also may enable assessment of disease progression and efficacy of therapy. Current data indicate that collagen-derived peptides represent one of the main peptidic components in urine, which are consistently found at reduced levels in diabetes. It is tempting to speculate that this decrease in urinary collagen-derived peptides is related to an increase in extracellular matrix deposition which is a major complication in diabetes. Therefore, urinary proteome analysis might enable noninvasive assessment of this process at an early stage via determination of specific collagen fragments. This may open an avenue towards targeted therapeutic intervention. [source]

Presence of CD4+CD8+ double-positive T cells with very high interleukin-4 production potential in lesional skin of patients with systemic sclerosis

ARTHRITIS & RHEUMATISM, Issue 10 2007
Yann Parel
Objective Fibrotic skin changes in systemic sclerosis (SSc) are preceded by the appearance of an inflammatory infiltrate rich in T cells. Since no direct comparison with T cells in normal skin has been performed previously, this study was undertaken to functionally characterize T cells in the skin of patients with early active SSc and in normal skin. Methods We characterized coreceptor expression, T cell receptor (TCR) usage, cytokine production, and helper and cytolytic activity of T cell lines and clones established from skin biopsy specimens from 6 SSc patients and 4 healthy individuals. Immunofluorescence analysis of skin biopsy and peripheral blood samples was performed to confirm the presence of specific subsets in vivo. Results A distinct subset expressing both CD4 and CD8,/, coreceptors at high levels (double-positive [DP]) was present in T cell lines from SSc and normal skin. DP T cells actively transcribed both accessory molecules, exerted clonally distributed cytolytic and helper activity, and expressed TCR clonotypes distinct from those in CD4+ or CD8+ single-positive (SP) T cells. In SSc skin, DP T cells produced very high levels of interleukin-4 (IL-4) compared with CD4+ SP T cells. Furthermore, DP T cells were directly identified in SSc skin, thus providing evidence that they are a distinct subset in vivo. Conclusion The present findings show that T cells with the unusual CD4+CD8+ DP phenotype are present in the skin. Their very high level of IL-4 production in early active SSc may contribute to enhanced extracellular matrix deposition by fibroblasts. [source]

High mobility group box chromosomal protein 1: A novel proinflammatory mediator in synovitis

ARTHRITIS & RHEUMATISM, Issue 10 2002
R. Kokkola
Objective High mobility group box chromosomal protein 1 (HMGB-1) is a ubiquitous chromatin component expressed in nucleated mammalian cells. It has recently and unexpectedly been demonstrated that stimulated live mononuclear phagocytes secrete HMGB-1, which then acts as a potent factor that causes inflammation and protease activation. Macrophages play pivotal roles in the pathogenesis of arthritis. The aim of this study was to determine whether synovial macrophage expression of HMGB-1 is altered in human and experimental synovitis. Methods Intraarticular tissue specimens were obtained from healthy Lewis rats, Lewis rats with Mycobacterium tuberculosis,induced adjuvant arthritis, and from patients with rheumatoid arthritis (RA). Specimens were immunohistochemically stained for cellular HMGB-1. Extracellular HMGB-1 levels were assessed in synovial fluid samples from RA patients by Western blotting. Results Immunostaining of specimens from normal rats showed that HMGB-1 was primarily confined to the nucleus of synoviocytes and chondrocytes, with occasional cytoplasmic staining and no extracellular matrix deposition. In contrast, inflammatory synovial tissue from rats with experimental arthritis as well as from humans with RA showed a distinctly different HMGB-1 staining pattern. Nuclear HMGB-1 expression was accompanied by a cytoplasmic staining in many mononuclear cells, with a macrophage-like appearance and an extracellular matrix deposition. Analysis of synovial fluid samples from RA patients further confirmed the extracellular presence of HMGB-1; 14 of 15 samples had HMGB-1 concentrations of 1.8,10.4 ,g/ml. Conclusion The proinflammatory mediator HMGB-1 was abundantly expressed as a nuclear, cytoplasmic, and extracellular component in synovial tissues from RA patients and from rats with experimental arthritis. These findings suggest a pathogenetic role for HMGB-1 in synovitis and indicate a new potential therapeutic target molecule. [source]

Aberrant serum hyaluronan and hyaluronidase levels in scleroderma

BRITISH JOURNAL OF DERMATOLOGY, Issue 3 2004
B.A. Neudecker
Summary Background Scleroderma, or systemic sclerosis, is characterized by aberrations of extracellular matrix deposition. These changes parallel early stages of wound healing when increased deposition of hyaluronan (HA) and collagen occur. Both processes result ultimately in the formation of fibrotic scar tissue. Activities of HA synthase and hyaluronidase, the enzymes that synthesize and degrade HA, are critical in HA turnover. Both become elevated whenever increased matrix deposition occurs. HA deposition occurs early in wound healing, and increases are documented in the circulation of scleroderma patients. We postulated that elevated HA and hyaluronidase may both be indicators of early-stage disease in scleroderma, in parallel with early changes observed in wound healing. In an attempt to reduce HA accumulation and the associated fibrosis in scleroderma tissues, topical and intravenous hyaluronidase administrations have been used in the past as treatment modalities, with occasional success. This also suggested that hyaluronidase enzyme activity is involved in the disease process. It is now recognized that the hyaluronidases constitute an enzyme family. The somatic hyaluronidase Hyal-1 is the only activity present in human serum. Objectives To determine levels of HA and Hyal-1 in the sera of scleroderma patients at various stages of their disease. Methods Levels of HA and Hyal-1 activity were determined in 25 scleroderma patients. Subjects were separated into two groups, those in the early stage with duration of disease of 2 years or less, and late-stage patients with disease duration of more than 2 years. Results In early-stage scleroderma, levels of HA were elevated significantly, as predicted, in comparison with late-stage patients and controls. Late-stage levels of HA were comparable with those found in control sera. By contrast, levels of Hyal-1 activity were normal in early-stage patients, similar to those in controls, but were decreased in late-stage patients, falling even below those of controls. Conclusions We have confirmed that circulating levels of HA are elevated in scleroderma, but show for the first time that such elevations occur predominantly in early-stage disease. Patients with late-stage disease have decreased serum Hyal-1 activity, perhaps reflecting decreased levels of HA turnover. This study also represents the first time that hyaluronidase activity levels have been determined in scleroderma patients. [source]