HGF as a renotrophic and anti-fibrotic regulator in chronic renal disease

Abstract

Hepatocyte growth factor (HGF) and Met/HGF receptor play roles in dynamic growth and morphogenesis during development and regeneration of organs, including the kidney. In the kidney, HGF targets different types of cells, while its biological actions depend on a target cell type. During the earlier stages of chronic renal failure, renal HGF expression increased, but in later stages HGF expression decreased, associated with manifestation of chronic renal failure. When anti-HGF IgG was administered into mice with chronic renal failure, renal dysfunction and fibrosis were accelerated, indicating a role of endogenous HGF to suppress chronic renal failure. For myofibroblasts, a key cell type in tissue fibrosis, HGF exerted biological activities, including (i) inhibition of growth, (ii) suppression of fibrogenic cytokine expression, and (iii) enhancement of matrix metalloproteinases involved in subsequent apoptosis. In models of glomerular and tubulo-interstitial fibrosis, administration of HGF or HGF gene therapy improved renal fibrosis and dysfunction. Since insufficient production of HGF is causative for renal fibrosis, supplementation with HGF represents a new approach to inhibit or improve chronic renal failure.