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Matrix Metalloproteinase Expression (matrix + metalloproteinase_expression)
Selected Abstracts2,3,4,,5-TETRAHYDROXYSTILBENE-2- O -,- d -GLUCOSIDE SUPPRESSES MATRIX METALLOPROTEINASE EXPRESSION AND INFLAMMATION IN ATHEROSCLEROTIC RATSCLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 3 2008Wei Zhang SUMMARY 1In coronary artery disease, the typical atheromatous plaque consists of a lipid core containing various inflammatory cells and a fibrous cap composed mostly of extracellular matrix. Both matrix metalloproteinases (MMPs) and inflammation are involved in the initiation of atherosclerotic plaques and plaque instability. 22,3,4¢,5-Tetrahydroxystilbene-2- O -b- d -glucoside (TSG) reduces the blood lipid content and prevents the atherosclerotic process, but the mechanism of action of TSG is unclear. The purpose of the present study was to test whether TSG can suppress MMP activation and inflammation in atherosclerotic rats. 3Sixty male Sprague-Dawley rats were randomly divided into six groups. Atherosclerosis was induced by feeding rats a hyperlipidaemic diet; TSG (120, 60 or 30 mg/kg per day) was administered by oral gavage. After 12 weeks of treatment, rats were killed (ethyl carbamate 1200 mg/kg) and serum lipids, C-reactive protein (CRP), interleukin (IL)-6 and tumour necrosis factor (TNF)-a were measured. Haematoxylin,eosin (H&E) staining was used to examine histopathological changes in the aorta. The mRNA and protein expression of MMPs were assayed by reverse transcription,polymerase chain reaction, immunohistochemistry and western blotting. Simvastatin (2 mg/kg per day) was administered as a positive control, whereas the vehicle (0.9% NaCl) group served as the untreated control. 4In the present study, TSG significantly and dose-dependently attenuated the hyperlipidaemic diet-induced alterations in serum lipid profile and increases in CRP, IL-6 and TNF-a levels. In addition, TSG normalized the structure of the aortic wall and suppressed the expression of MMP-2 and MMP-9 at both the mRNA and protein level in the rat aortic wall. 5In summary, TSG suppresses the expression of MMP-2 and MMP-9 and inhibits inflammation in the diet-induced atherosclerotic rats. [source] Complete Compilation of Matrix Metalloproteinase Expression in Human Decidua during PregnancyAMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 3 2007J Stojic No abstract is available for this article. [source] Enhancement of intervertebral disc cell senescence by WNT/,-catenin signaling,induced matrix metalloproteinase expressionARTHRITIS & RHEUMATISM, Issue 10 2010Akihiko Hiyama Objective To determine whether intervertebral disc (IVD) cells express ,-catenin and to assess the role of the WNT/,-catenin signaling pathway in cellular senescence and aggrecan synthesis. Methods The expression of ,-catenin messenger RNA (mRNA) and protein in rat IVD cells was assessed by using several real-time reverse transcription,polymerase chain reaction, Western blot, immunohistochemical, and immunofluorescence analyses. The effect of WNT/,-catenin on nucleus pulposus (NP) cells was examined by transfection experiments, an MTT assay, senescence-associated ,-galactosidase staining, a cell cycle analysis, and a transforming growth factor (TGF,)/bone morphogenetic protein (BMP) pathway,focused microarray analysis. Results We found that ,-catenin mRNA and protein were expressed in discs in vivo and that rat NP cells exhibited increased ,-catenin mRNA and protein upon stimulation with lithium chloride, a known activator of WNT signaling. LiCl treatment inhibited the proliferation of NP cells in a time- and dose-dependent manner. In addition, there was an increased level of cellular senescence in LiCl-treated cells. Long-term treatment with LiCl induced cell cycle arrest and promoted subsequent apoptosis in NP cells. Activation of WNT/,-catenin signaling also regulated the expression of aggrecan. We also demonstrated that WNT/,-catenin signaling induced the expression of matrix metalloproteinases (MMPs) and TGF, in NP cells. Conclusion The activation of WNT/,-catenin signaling promotes cellular senescence and may modulate MMP and TGF, signaling in NP cells. We hypothesize that the activation of WNT/,-catenin signaling may lead to an increased breakdown of the matrix, thereby promoting IVD degeneration. [source] Role of Wnt-5A in interleukin-1,,induced matrix metalloproteinase expression in rabbit temporomandibular joint condylar chondrocytesARTHRITIS & RHEUMATISM, Issue 9 2009Xianpeng Ge Objective To determine the possible involvement and regulatory mechanisms of Wnt-5A signaling in interleukin-1, (IL-1,),induced increase in matrix metalloproteinase 1 (MMP-1), MMP-3, MMP-9, and MMP-13 expression in temporomandibular joint (TMJ) condylar chondrocytes. Methods Primary rabbit condylar chondrocytes were treated with IL-1,, purified Wnt-5A protein, or both and transfected with Wnt-5A expression vector. Expression of Wnt-5A, MMP-1, MMP-3, MMP-9, MMP-13, and type II collagen, as well as cell morphologic changes, were examined. To explore the mechanisms of action of Wnt-5A, the accumulation and nuclear translocation of ,-catenin, the transcription activity of the ,-catenin,Tcf/Lef complex, phosphorylated JNK, phosphorylated ERK, and phosphorylated p38 were analyzed. SP600125, a JNK inhibitor, was used to investigate the role of the JNK pathway in Wnt-5A induction of MMP-1, MMP-3, MMP-9, and MMP-13. Results Treatment of rabbit condylar chondrocytes with IL-1, up-regulated Wnt-5A expression. Purified Wnt-5A protein and transfection with Wnt-5A expression vector promoted the expression of MMP-1, MMP-3, MMP-9, and MMP-13. Wnt-5A did not cause accumulation and nuclear translocation of ,-catenin or activation of the ,-catenin-Tcf/Lef transcription complex. Instead, Wnt-5A activated JNK, and an inhibitor of JNK blocked the Wnt-5A,induced up-regulated expression of MMPs. Conclusion These findings indicate that IL-1, up-regulates Wnt-5A, and the activation of Wnt-5A signaling induces the expression of MMP-1, MMP-3, MMP-9, and MMP-13 via the JNK signaling pathway in rabbit TMJ condylar chondrocytes. Blockage of JNK signaling impairs the Wnt-5A,induced up-regulation of MMPs. Thus, Wnt-5A may be associated with cartilage destruction by promoting the expression of MMPs. [source] The ,7 nicotinic acetylcholine receptor on fibroblast-like synoviocytes and in synovial tissue from rheumatoid arthritis patients: A possible role for a key neurotransmitter in synovial inflammationARTHRITIS & RHEUMATISM, Issue 5 2009Marjolein A. Van Maanen Objective Recent studies have suggested an important role for neurotransmitters as modulators of inflammation. Therefore, we undertook this study to investigate the expression of the ,7 subunit of the nicotinic acetylcholine receptor (,7nAChR) and its function in rheumatoid arthritis (RA). Methods The potential role of the ,7nAChR in modulating proinflammatory cytokine expression in fibroblast-like synoviocytes (FLS) was identified by screening an adenoviral short hairpin RNA (Ad.shRNA) library. An ,7-specific antibody was used for immunohistochemistry, and fluorescein isothiocyanate,labeled ,-bungarotoxin, which binds specifically to the ,7nAChR, was used for immunofluorescence. Gene expression in FLS was determined by quantitative polymerase chain reaction with primers specific for the ,7nAChR. In addition, we analyzed messenger RNA (mRNA) expression of dup,7, a variant ,7 transcript. Next, we studied the functional role of the ,7nAChR in RA FLS by examining the effects of ,7-specific agonists on the production of interleukin-6 (IL-6) and IL-8 by activated FLS. Results A screen using an Ad.shRNA library against 807 transcripts revealed that a specific ,7nAChR shRNA potently modulated IL-8 and matrix metalloproteinase expression in FLS. The ,7nAChR was expressed in the inflamed synovium from RA patients, predominantly in the intimal lining layer. We found ,7nAChR expression at both the mRNA and protein level in cultured RA FLS. FLS also constitutively expressed dup,7 mRNA. Specific ,7nAChR agonists reduced tumor necrosis factor ,,induced IL-6 and IL-8 production by FLS. Conclusion The ,7nAChR and its dup,7 variant are expressed in RA synovium, where they may play a critical role in regulating inflammation. Targeting the ,7nAChR could provide a novel antiinflammatory approach to the treatment of RA. [source] Curcumin: potential for hepatic fibrosis therapy?BRITISH JOURNAL OF PHARMACOLOGY, Issue 3 2008M A O'Connell The beneficial antioxidative, anti-inflammatory and antitumorigenic effects of curcumin have been well documented in relation to cancer and other chronic diseases. Recent evidence suggests that it may be of therapeutic interest in chronic liver disease. Hepatic fibrosis (scarring) occurs in advanced liver disease, where normal hepatic tissue is replaced with collagen-rich extracellular matrix and, if left untreated, results in cirrhosis. Curcumin inhibits liver cirrhosis in a rodent model and exerts multiple biological effects in hepatic stellate cells (HSCs), which play a central role in the pathogenesis of hepatic fibrosis. In response to liver injury, these cells proliferate producing pro-inflammatory mediators and extracellular matrix. Curcumin induces apoptosis and suppresses proliferation in HSCs. In addition, it inhibits extracellular matrix formation by enhancing HSC matrix metalloproteinase expression via PPAR, and suppressing connective tissue growth factor (CTGF) expression. In this issue, Chen and co-workers propose that curcumin suppresses CTGF expression in HSC by inhibiting ERK and NF-,B activation. These studies suggest that curcumin modulates several intracellular signalling pathways in HSC and may be of future interest in hepatic fibrosis therapy. British Journal of Pharmacology (2008) 153, 403,405; doi:10.1038/sj.bjp.0707580; published online 26 November 2007 [source] | ||||||||||