Hepatocyte growth factor inhibits TGF-β1-induced proliferation, transformation, and secretory function of cardiac fibroblasts by activating the c-Met-Akt-TGIF signaling pathway.
Does hepatocyte growth factor (HGF) prevent TGF-β1-induced proliferation, differentiation, and secretory function in neonatal rat cardiac fibroblasts?
HGF negatively regulates TGF-β1-induced cardiac fibroblast proliferation and transformation into myofibroblasts via the c-Met-Akt-TGIF signaling pathway, suggesting a potential therapeutic mechanism against cardiac fibrosis.
valor p: p=<0.05
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‑β1 (TGF‑β1). HGF expression levels were significantly reduced in the CFs following treatment with 5 ng/ml TGF‑β1 for 48 h. The overexpression of HGF suppressed the proliferation, transformation and the secretory function of the CFs following treatment with TGF‑β1, as indicated by the attenuated expression levels of α-smooth muscle actin (α‑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‑β1 stimulation.
Yi et al. (Fri,) conducted a other in Cardiac fibrosis. Hepatocyte growth factor (HGF) overexpression or knockdown vs. AdGFP or AdshRNA control was evaluated on Cardiac fibroblast proliferation, transformation, and secretory function (p=<0.05). Hepatocyte growth factor inhibits TGF-β1-induced proliferation, transformation, and secretory function of cardiac fibroblasts by activating the c-Met-Akt-TGIF signaling pathway.