Journal
INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE
Volume 34, Issue 2, Pages 381-390Publisher
SPANDIDOS PUBL LTD
DOI: 10.3892/ijmm.2014.1782
Keywords
hepatocyte growth factor; cardiac fibroblasts; fibrosis; c-Met; Akt
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Funding
- National Natural Science Foundation of China [81170307]
- National Key Basic Research Program of China [2011CB606202]
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Cardiac fibroblast (CF) proliferation and transformation into myofibroblasts play important roles in cardiac fibrosis during pathological myocardial remodeling. In this study, we demonstrate that hepatocyte growth factor (HGF), an antifibrotic factor in the process of pulmonary, renal and liver fibrosis, is a negative regulator of cardiac fibroblast transformation in response to transforming growth factor-beta(1) (TGF-beta(1)). HGF expression levels were significantly reduced in the CFs following treatment with 5 ng/ml TGF-beta(1) for 48 h. The over-expression of HGF suppressed the proliferation, transformation and the secretory function of the CFs following treatment with TGF-beta(1), as indicated by the attenuated expression levels of a-smooth muscle actin (alpha-SMA) and collagen I and III, whereas the knockdown of HGF had the opposite effect. Mechanistically, we identified that the phosphorylation of c-Met, Akt and total protein of TGIF was significantly inhibited by the knockdown of HGF, but was significantly enhanced by HGF overexpression. Collectively, these results indicate that HGF activates the c-Met-Akt-TGIF signaling pathway, inhibiting' CF proliferation and transformation in response to TGF-beta(1) stimulation.
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