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Molecular Mechanisms of PDGF‐D‐Induced Cardiac Fibrogenesis
Author(s) -
Zhao Tieqiang,
Zhao Wenyuan,
Chen Yuanjian,
Li Victoria S,
Sun Yao
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.1129.12
Subject(s) - platelet derived growth factor receptor , fibroblast , platelet derived growth factor , growth factor , matrix metalloproteinase , endocrinology , myofibroblast , chemistry , transforming growth factor , medicine , fibroblast growth factor , tissue inhibitor of metalloproteinase , microbiology and biotechnology , receptor , biology , fibrosis , in vitro , biochemistry
Our previous study showed that Platelet‐derived growth factor (PDGF)‐D and its receptors PDGFR‐β are significantly increased in fibroblasts of the infarcted heart. The role of PDGF‐D on cardiac fibrogenesis remains unknown and is explored in this study. Methods and Results Cardiac fibroblasts were isolated from Sprague Dawley rats and treated with PDGF‐D for 24 hr. The effect of PDGF‐D on fibroblast growth, phenotype change, collagen synthesis and degradation were investigated. Compared to controls, fibroblast proliferation increased six‐fold in cells treated with PDGF‐D. PDGF‐D stimulates fibroblast differentiation into myofibroblasts. PDGF‐D treatment significantly enhanced type I collagen secretion. Matrix metalloproteinase (MMP)‐1, MMP‐2 and MMP‐9 levels were also significantly elevated by PDGF‐D treatment, which were coincident with increased expressions of tissue inhibitor of metalloproteinase (TIMP)‐1 and TIMP‐2. Finally, PDGF‐D significantly enhanced transforming growth factor (TGF)‐β1 synthesis in fibroblasts. Conclusions These observations indicate that PDGF‐D promotes cardiac fibrogenesis by stimulating fibroblast proliferation, differentiation and collagen synthesis. Co‐elevations of MMPs and TIMPs counteract the effect of PDGF‐D on collagen degradation. The fibrogenic role of PDGF‐D in cardiac fibroblasts may be mediated through activating TGF‐ β1 pathway.