Effect Of GLP-1Analogues On The Expression Of Connective Tissue Growth Factor (CTGF) And Bone Morphogenetic Protein-7(BMP-7) In Human Renal Tubular Epithelial Cell Cultured With High Concentration Of D-glucose

Objective:To study the expression of connective tissue growth factor (CTGF) and bone morphogenetic protein-7(BMP-7) in human renal tubular epithelial cell cultured in high-glucose environment and to reveal the effect of high glucose on human renal tubular epithelial cells.Methods:HK-2cells were subcultured under normal glucose (NG), mannitol glucose (MG) and high glucose(HG).The mRNA and protein of CTGF and BMP-7were detected with immunocytochemistry and Real-time PCR at24,48,72h respectively to help choosing suitable time for the research.Result:Compared with the normal groups, the expression of CTGF mRNA and protein significantly increased in the high glucose group at24h、48h and72h (P＜0.01).The mRNA levels reached a peak at48h, protein expression continue increased until to72h.the expression of BMP-7mRNA and protein significantly decreased in the high glucose group at24h、48h and72h in time-dependent manner(P<0.05).Conclusion:High glucose stimulates production of CTGF,ruduce the expression of BMP-7, which may help explain the importance of CTGF and BMP-7on renal lesions in high-glucose environment. Objective:To study the effect of exendin-4of GLP-1analogues on on the expression of connective tissue growth factor (CTGF) and bone morphogenetic protein-7(BMP-7) in human renal tubular epithelial cell cultured in high-glucose environment and to investigate the possible effect and mechanism of GLP-1on renal lesions in high-glucose environment.Methods:HK-2cells were cultured with different concentration of exendin-4and the cell proliferation was examined by MTT to determine suitable experimental dose of exendin-4.HK-2cells were subcultured under normal glucose (NG),high glucose (HG)and high glucose with different concentrations of exendin-4group (including exendin-410,20,40pmol/L). The activity of CTGF and the expressions of BMP-7mRNA and protein in cultured HK-2cells were detected with immunocytochemistry and Real-time PCR at48h.Result:1.Compared with the normal group, the cell proliferation slightly high in Exendin-4with0.1pmol/L,1.Opmol/L,10pmol/L,50pmol/L,but there are no significant difference (p>0.05). The cell proliferation in Exendin-4with100pmol/L was higher than that in the normal group(p<0.05);The cell proliferation in Exendin-4with200pmol/L,1000pmol/L Significantly higher than that in the normal group (p<0.05).2.Compared with the high glucose groups, the expressions of CTGF mRNA and protein were lower in all the exendin-4groups at48h in dose-dependent manne(P＜0.05); the expressions of BMP-7mRNA and protein increased in all the exendin-4groups at48h in dose-dependent manne(P＜0.01).Conclusion:Exendin-4may improve the damage of renal tubular epithelial cells by inhibit the expression of CTGF and increase the expression of BMP-7in high glucose-induced HK-2cells.