Hepatocyte growth factor regulates the TGF-β1-induced proliferation, differentiation and secretory function of cardiac fibroblasts.

Abstract

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.

• Authors: Xin Yi, Xiaoyan Li, Yanli Zhou, Shan Ren, Weiguo Wan, Gaoke Feng, Xuejun Jiang
• Journal: International journal of molecular medicine (Int J Mol Med) Vol. 34 Issue 2 Pg. 381-90 (Aug 2014) ISSN: 1791-244X [Electronic] Greece
• PMID: 24840640 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Transforming Growth Factor beta1
• Hepatocyte Growth Factor
• Proto-Oncogene Proteins c-met
• Oncogene Protein v-akt

Topics

• Animals
• Cell Differentiation (genetics)
• Cell Proliferation (genetics)
• Gene Expression Regulation
• Gene Knockdown Techniques
• Heart Failure (genetics, metabolism, pathology)
• Hepatocyte Growth Factor (biosynthesis, genetics)
• Humans
• Myofibroblasts (metabolism, pathology)
• Oncogene Protein v-akt (genetics, metabolism)
• Proto-Oncogene Proteins c-met (genetics, metabolism)
• Rats
• Signal Transduction
• Transforming Growth Factor beta1 (biosynthesis, metabolism)