Hepatocyte growth factor ameliorates progression of interstitial injuries in tubular epithelial cells

Hepatocyte growth factor (HGF) and its c-met receptor comprise a signalling system that has been reported to prevent injury in several models of renal disease; however, whether HGF can also retard progression of chronic kidney disease is not known. The aim of the present study was to examine the effects of HGF on progression of chronic kidney disease in tubular epithelial cells.

Studies were performed in human tubular epithelial cells that underwent different glucose concentrations, and then receive HGF or vehicle. The cell apoptosis was tested by DAPI and TUNEL staining. The level of activity of HGF was examined at multiple time-points. The expression of HGF, transforming growth factor-beta(1) (TGF-beta(1)), plasminogen activator inhibitor-1 (PAI-1) and collagen IV were examined by reverse transcription-polymerase chain reaction, Western blot and enzyme-linked immunosorbent assay.

HGF administration was associated with a reduction in TGF-beta(1). The beneficial effects of HGF were associated with reductions in the expression of TGF-beta(1), and in the extent of epithelial cell apoptosis. HGF appeared to induce fibrinolytic pathways by reducing the expression of collagen IV and decreasing levels of PAI-1.

These findings suggest that HGF can retard progression of diabetic nephropathy, primarily by promoting matrix degradation, and that HGF is a potent antifibrogenic factor.