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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