Hepatocyte growth factor modulates H2O2-induced mesangial cell apoptosis through induction of heme oxygenase-1.

Oxidative stress plays an important role in the induction of mesangial cell (MC) injury. In the present study, we evaluated the molecular mechanism involved in hydrogen peroxide (H2O2)-induced MC apoptosis. In addition, we examined the role of heme oxygenase-1 (HO-1) in hepatocyte growth factor (HGF)-modulated, H2O2-induced MC injury. H2O2 promoted (p < 0.001) mouse MC (MMC) apoptosis. This effect of H2O2 was associated with translocation of cytochrome c from the mitochondrial to the cytosolic compartment. In addition, a caspase-9 inhibitor partially attenuated this effect of H2O2. These findings suggest that H2O2-induced MMC apoptosis is mediated through the mitochondrial pathway. HGF not only prevented H2O2-induced MMC apoptosis, but also inhibited H2O2-induced translocation of cytochrome c from the mitochondrial to the cytosolic compartment. HGF also promoted the expression of HO-1 by MMCs; interestingly, hemin inhibited (p < 0.001) H2O2-induced MMC apoptosis. On the other hand, zinc protoporphyrin inhibited the protective influence of HGF on H2O2-induced MMC apoptosis. These findings suggest that H2O2-induced apoptosis occurs through the mitochondrial pathway. HGF provides protection against H2O2-induced MMC apoptosis through induction of HO-1. Copyright 2005 S. Karger AG, Basel.