Hepatocyte growth factor protection of retinal pigment epithelial cells

Hepatocyte growth factor (HGF) is a pleiotropic growth factor that is mainly expressed in mesenchymal cells. MET (mesenchymal-epithelial transition factor) is a membrane receptor that binds HGF. The receptors for HGF (MET) are primarily found in epithelial cells and several stromal cells. Activation of MET by HGF promotes migration, mitosis, and survival of various cells. HGF protects various cells from oxidative stress-induced apoptosis mainly via the phosphorylation of phosphoinositide 3-kinase/Akt pathway. HGF also plays a role in embryogenesis, tissue repair, and angiogenesis. HGF levels in the ocular fluids are elevated in various ocular diseases related to cell proliferation and angiogenesis. HGF protects retinal pigment epithelial (RPE) cells from hydrogen peroxide-induced apoptosis by inhibition of the mitochondrial apoptotic pathway. In ceramide- and glutathione depletion-induced apoptosis of RPE cells, studies have also demonstrated that HGF can protect RPE cells in these oxidative stress models. These studies suggest that HGF is a natural protective factor for RPE cells and plays an autocrine role protecting RPE cells against oxidative stress.