title: Matrix metalloproteinase-9 induces cardiac fibroblast migration, collagen and cytokine secretion: inhibition by salvianolic acid B from Salvia miltiorrhiza.
abstract: 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. 200 nM 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±0.1 pg/ml, p<0.05) and down-regulated VEGF (436.5±148.9 versus 1034.3±28.1 pg/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.affiliation: Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai Zhangjiang Hitech Park, Haike Road #501, Shanghai 201203, China.
authors.forename: Yanhui
authors.initials: Y
authors.lastname: Wang
authors.forename: Feng
authors.initials: F
authors.lastname: Xu
authors.forename: Jing
authors.initials: J
authors.lastname: Chen
authors.forename: Xu
authors.initials: X
authors.lastname: Shen
authors.forename: Yanping
authors.initials: Y
authors.lastname: Deng
authors.forename: Lingling
authors.initials: L
authors.lastname: Xu
authors.forename: Jun
authors.initials: J
authors.lastname: Yin
authors.forename: Hui
authors.initials: H
authors.lastname: Chen
authors.forename: Fukang
authors.initials: F
authors.lastname: Teng
authors.forename: Xuan
authors.initials: X
authors.lastname: Liu
authors.forename: Wanying
authors.initials: W
authors.lastname: Wu
authors.forename: Baohong
authors.initials: B
authors.lastname: Jiang
authors.forename: De-an
authors.initials: DA
authors.lastname: Guo
mesh_terms: D000818:Animals; D001572:Benzofurans / Q000737:chemistry / Q000494:pharmacology*; D002465:Cell Movement / Q000187:drug effects* / Q000502:physiology; D003094:Collagen / Q000096:biosynthesis*; D016207:Cytokines / Q000096:biosynthesis*; D004790:Enzyme Induction; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism / Q000494:pharmacology*; D061965:Matrix Metalloproteinase Inhibitors; D008518:Medicine, East Asian Traditional; D009206:Myocardium / Q000166:cytology* / Q000378:metabolism; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology; D017434:Protein Structure, Tertiary; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins / Q000378:metabolism / Q000494:pharmacology; D027561:Salvia miltiorrhiza / Q000737:chemistry; D015854:Up-Regulation / Q000187:drug effects; D053630:Depsides
chemical_list: D001572:Benzofurans; D003094:Collagen; D016207:Cytokines; D020780:Matrix Metalloproteinase 9; D061965:Matrix Metalloproteinase Inhibitors; D010936:Plant Extracts; D011994:Recombinant Proteins; C076944:salvianolic acid B; D053630:Depsides