The HGF/c-Met Receptor System Under Pathological Conditions

Author(s): Yoshiaki Taniyama, Junya Azuma, Kazuma Iekushi, Fumihiro Sanada, Masaaki Iwabayashi, Hiroshi Kusunoki, Keita Okayama, Rei Otsu, Hiromi Rakugi, Ryuichi Morishita.

Journal Name: Immunology, Endocrine & Metabolic Agents in Medicinal Chemistry (Under Re-organization)

Volume 12 , Issue 2 , 2012

Abstract:

Hepatocyte growth factor (HGF) is a mesenchyme-derived pleiotropic factor which regulates cell growth, cell motility, and morphogenesis of various types of cells, and is thus considered a humoral mediator of morphogenic tissue interactions. Although HGF was originally identified as a potent mitogen for hepatocytes, it has also been identified as a member of angiogenic growth factors. Interestingly, the presence of its specific receptor, c-met, is observed not only in hepatocyte but also in vascular cells, cardiac myocytes, skeletal muscle, kidney cells, neuronal cell, and fibroblasts. On the other hand, vascular endothelial growth factor (VEGF) is also a growth factor for endothelial cells. The signal transduction of VEGF and HGF is quite similar in physiological condition, but differs in pathological condition. To investigate this difference between HGF and VEGF, we showed that HGF but not VEGF prevents the senescence EPC due to oxidative stress through the inhibition of rac1. Moreover, we reported that HGF promotes SHIP-2 translocation from epithelial growth factor receptor (EGFR) to c-Met, and protects oxidative stress through EGFR degradation. By this anti-oxidative and anti-senescence effects of HGF would maintain the vessels long enough in patients receiving much oxidative stress. Another unique effect of HGF is anti-fibrosis. HGF does not inhibit TGF-β1 in physiological condition, but reduces it in pathological, we discuss the potential effect of condition by promoting the myofibroblast apoptosis, and inhibits the vicious cycle of TGF-β1 and angiotensin II through the inhibition of PTEN activity.

In this report HGF on pathological condition in cardiovascular diseases and chronic kidney disease (CKD).

Keywords: Angiogenesis, c-Met, PTEN, epithelial growth factor receptor (EGFR), fibroblast growth factor (FGF), fibrosis, gene therapy, hepatocyte growth factor (HGF), peripheral artery disease (PAD), senescence, TGF-beta, vascular endothelial growth factor (VEGF)

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Article Details

VOLUME: 12
ISSUE: 2
Year: 2012
Page: [122 - 129]
Pages: 8
DOI: 10.2174/187152212800389030
Price: $58

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