Hepatocyte Growth Factor and Kidney Disease / 대한신장학회지

ABSTRACT

Hepatocyte growth factor (HGF), also known as scatter factor, was identified during the experimental attempts to explore a phantom factor acting as a trigger for liver regeneration after partial hepatecotmy. HGF is synthesized and secreted as a single-chain inert precursor by cells of mesodermal origin, and extracellularly processed to the two-chain functional heterodimer by proteolytic cleavage at a specific site. The binding of HGF to the c-MET, the HGF receptor, induces activation of tyrosine kinase and autophosphorylation of tyrosine residues. c-MET activation propagates an intricate system of signaling pathways that controls a range of cellular processes as diverse as cell proliferation, differentiation, transformation and apoptosis. In the aspect of kidney, the HGF/c-MET signaling pathway plays important roles in renal development and in the maintenance of normal adult kidney structure and function. In various injury and disease models, HGF has been reported to promote cell survival, tissue regeneration, and fibrosis suppression. Neutralization of HGF by the antibody may accelerate renal failure or fibrosis while HGF administration may lead to remarkable amelioration. Thus, HGF is not only the endogenous safeguard protecting normal tissues against the fibrotic process after injury, but also a therapeutic option to prevent organ failure. If insufficient production of HGF is causative for renal fibrosis, administration of recombinant human HGF protein or HGF gene therapy may improve renal fibrosis and dysfunction. HGF gene therapy requires appropriate delivery systems, and biodegradable polyester amine based on glycerol dimethacrylate and polyethylenimine is being tested for the HGF gene carrier in experimental models.