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


METHODS
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.


RESULTS
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.


CONCLUSIONS
These findings suggest that HGF can retard progression of diabetic nephropathy, primarily by promoting matrix degradation, and that HGF is a potent antifibrogenic factor.
Mou
Shan
S
Renal Division, Renji Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, China.
Wang
Qin
Q
Shi
Beili
B
Gu
Leyi
L
Ni
Zhaohui
Z
D002478:Cells, Cultured; D002908:Chronic Disease; D018450:Disease Progression; D004847:Epithelial Cells; D017228:Hepatocyte Growth Factor / Q000627:therapeutic use*; D006801:Humans; D007674:Kidney Diseases / Q000517:prevention & control*; D007684:Kidney Tubules; D053773:Transforming Growth Factor beta1 / Q000096:biosynthesis
D053773:Transforming Growth Factor beta1; D017228:Hepatocyte Growth Factor