OBJECTIVETo observe the effect of high glucose exposure on connective tissue growth factor (CTGF) expression in cultured human renal tubular epithelial cells and investigate the role of p38MAPK pathway in this process.

METHODSHuman renal tubular epithelial cells (HKC) with and without SB203580 pretreatment were cultured in the presence of high glucose levels for 24, 48, 72, 96 h and 20 days. RT-PCR, immunohistochemical staining, indirect fluorescence staining and Western blotting were used to detect the changes in CTGF mRNA and protein expressions in the cells after the treatment.

RESULTSLow levels of CTGF mRNA and protein were detected in cultured HKC cells, and after high glucose treatment, the mRNA expression increased gradually and reached the peak level at 48 h, then followed by gradual decrease till recovering the baseline level at 96 h. Prolonged high glucose treatment for 20 days resulted in persisted high CTGF mRNA expression twice the level in the control group. The expression level of CTGF protein also increased progressively as the treatment time then prolonged, and long-term (20 days) treatment increased the expression by 4 folds in comparison with the expression in the control cells. SB203580 significantly inhibited the increase in the expressions of CTGF mRNA and protein stimulated by high glucose treatment.

CONCLUSIONHigh glucose treatment can increase CTGF mRNA and protein expressions in cultured human renal tubular epithelial cells, suggesting that increased CTGF levels is a key event in the pathogenesis of renal tubulo-interstitial fibrosis in patients with diabetic nephropathy. p38MAPK pathway may also participate in this process.