Inhibitory effect of rapamycin on human renal tubular epithelial-myofibroblast transition / 基础医学与临床

ABSTRACT

Objective Rapamycin (RAPA) is an anti-proliferative immunosuppressant and has been used to suppress rejection of transplanted organs. In present study, we observed the effect of rapamycin on epithelial-myofibroblast transition (EMT)of cultured HKC cells in vitro. Methods Cultured human proximal tubular epithelial cells (HKCs) were divided into three groups blank control, treated with TGF-?1 (1 ?g/L) and treated with TGF-?1 (1 ?g/L) plus rapamycin (0.1, 1, 10, 100 ?g/L). The protein and mRNA for ?-SMA and E-cadherin in HKC cells were determined by Western Blot and RT-PCR.The mRNA level of Snail in HKC was detected by RT-PCR. Results Rapamycin dramatically abrogated TGF-?1 induced ?-SMA expression and restored E-cadherin expressionin HKC cells in a dose-dependent manner. At a concentration of 100 ?g/L, rapamycin almost completely blocked ?-SMA mRNA and protein expression induced by TGF-?1(1 ?g/L). Rapamycin also suppressed expression of ?-SMA in HKC cells at both mRNA and protein level in a time dependent manner.We also found rapamycin dramatically abrogated TGF-?1 induced Snail mRNA expression in HKC cells in a dose-dependent manner. Conclusion Rapamycin may inhibit EMT of tubular cells in vitro. The downregulation of Snail expression might be one of the mechanisms of rapamycin blocking EMT.