Expression of c-met stimulated by high glucose in human renal tubular epithelial cells and its implication

Abstract

The expression of c-met stimulated by high glucose in human renal tubular epithelial cells and the role of HGF/c-met system in diabetic nephropathy were examined. The proximal tubular epithelial cells were cultured in vitro under different conditions. MTT was used for the detection of cellular proliferation and RT-PCR was employed for measurement of c-met mRNA level. Our results showed that under different conditions, there were no significant differences in the proliferation of proximal tubular epithelial cells 12 h and 24 h after the culuture (P>0.05). The proliferation of proximal tubular epithelial cells showed a significant change 96 h after the culture and the cellular proliferation induced by hepatocyte growth factor (HGF) was very active (P<0.05). Moreover, no significant difference in the expression of c-met mRNA was found 12 h after the culture under different conditions (P>0.05), while 24 and 96 h after the culture, a persistent and significantly higher expression of c-met mRNA was found in HGF-induced proliferation. It is concluded that addition of exogenous HGF could inhibit the apoptosis induced by high-level glucose, promote the proliferation of proximal tubular epithelial cells, and induce the expression of c-met. Our study suggests that local up-regulation of HGF/c-met system plays an important role in the repair of renal damage in diabetic nephropathy.

Keywords

diabetic nephropathy / hepatocyte growth factor (HGF) / HGF receptor / receptor ligand system

References

[1] MatsumotoK., NakamuraT.. Hepatocyte growth factor: renotropic role and potential therapeutics for renal disease. Kidney Int, 2001, 59(5): 2023-2038

[2] NakamuraT., NishizawaT., HagiyaM., et al.. Molecular cloning and expression of human hepatocyte growth factor. Nature, 1994, 342(6248): 440-443

[3] MizunoS., MatsumotoK., KurosawaT., et al.. Reciprocal balance of hepatocyte growth factor and transforming growth factor-β 1 in renal fibrosis in mice. Kidney International, 2000, 57(3): 937-948

[4] WangS. N., LapageJ., HirschbergR.. Role of glomerular ultrafiltration of growth factor in progressive interstitial fibrosis in diabetic nephropathy. Kidney Int, 2000, 57(3): 1002-1014

[5] WenX. Y., ZhenF. L.. A preliminary study on the inhibitory effect of hepatocyte growth factor on the transdifferentiation of tubular epithelia. Chin J Intergr Tradit West Nephrol (Chinese), 2002, 3(7): 380-382

[6] MizunoS., KurosawaT., MatsumotoK., et al.. Hepatocyte growth factor prevents renal fibrosis and dysfunction in a mouse model of chronic renal disease. J Clin Invest, 1998, 101(9): 1827-1834

[7] KobayashiE., SasamuraH., MifuneM., et al.. Hepatocyte growth factor regulates proteoglycan synthesis in interstitial fibroblasts. Kidney Int, 2003, 64(4): 1179-1188

[8] LiuY., RajurK., TolbertE., et al.. Endogenous hepatocyte growth factor ameliorates chronic renal injury by activating matrix degradation pathways. Kidney Int, 2000, 58(5): 2028-2043

[9] MouS., ZhangQ. Y., ZhaoH. F., et al.. Expression of hepatocyte growth factor and c-met stimulated by high glucose in human kidney fibroblast and its significance. Chin J Endocrinol (Chinese), 2002, 18(4): 260-263

[10] CruzadoJ. M., LloherasN., TorrasJ., et al.. Regression of advanced diabetic nephropathy by hepatocyte growth factor gene therapy in rats. Diabetes, 2004, 53(4): 1119-1127

[11] DaiC., LiY., YangJ., et al.. Hepatocyte growth factor preserves beta cell mass and mitigates hyperlycemia in streptozotocin-induced diabetic mice. J Biol Chem, 2003, 278(27): 80-87