Document Detail


Matrix metalloproteinase-9 induces cardiac fibroblast migration, collagen and cytokine secretion: Inhibition by salvianolic acid B from Salvia miltiorrhiza.
MedLine Citation:
PMID:  21925853     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Cardiac fibroblasts play the key role in cardiac function and matrix metalloproteinases-9 (MMP-9) is a well known contributor to the development of myocardial remodeling. However, the direct regulation of MMP-9 on the function of cardiac fibroblasts and the underlying mechanism are far from elucidation. In the present research, recombinant protein encoding catalytic domain of MMP-9 (MMP-9 CD) was constructed and the function of neonatal cardiac fibroblasts was investigated by cell proliferation assay, migration assay, picrosirius red assay, multiplex cytokine assay and fibroblast phenotype detection. 200nM MMP-9 CD stimulated cardiac fibroblasts migration (169.4±22.5% versus 100±0%, p<0.01), increased collagen synthesis (1.5±0.2 fold, p<0.05), up-regulated the secretion of ICAM (574.0±40.1 versus 268.5±8.6pg/ml, p<0.01), TNF-α (192.6±11.0 versus 14.4±1.8pg/ml, p<0.001), IL-6 (1500.9±70.2 versus 323.4±40.6pg/ml, p<0.001) and sVCAM-1 (30.3±4.3 versus 7.0±0.1pg/ml, p<0.05) and down-regulated VEGF (436.5±148.9 versus 1034.3±28.1pg/ml, p<0.05) significantly with modest effects on proliferation. Accompanying with these regulations, transition of fibroblasts to myofibroblast was confirmed by immunofluorescent stain of α-smooth muscle actin (α-SMA) with MMP-9 CD treatment. Furthermore, salvianolic acid B (SalB) inhibited the effects of MMP-9 CD significantly. In conclusion, our results provide evidence for a direct influence of MMP-9 on cardiac fibroblast migration, collagen and cytokine secretion, which can be attenuated by SalB.
Authors:
Yanhui Wang; Feng Xu; Jing Chen; Xu Shen; Yanping Deng; Lingling Xu; Jun Yin; Hui Chen; Fukang Teng; Xuan Liu; Wanying Wu; Baohong Jiang; De-An Guo
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-9-16
Journal Detail:
Title:  Phytomedicine : international journal of phytotherapy and phytopharmacology     Volume:  -     ISSN:  1618-095X     ISO Abbreviation:  -     Publication Date:  2011 Sep 
Date Detail:
Created Date:  2011-9-19     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9438794     Medline TA:  Phytomedicine     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2011 Elsevier GmbH. All rights reserved.
Affiliation:
Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai Zhangjiang Hitech Park, Haike Road #501, Shanghai 201203, China; Shenyang Pharmaceutical University, Wenhua Road #103, Shenyang 110016, China.
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