Effects of high glucose on the expression of cytokines in renal proximal tubular epithelial cells in vitro / 基础医学与临床

ABSTRACT

Objective To investigate the effect of high glucose on the expression of transforming growth factor-?1(TGF-?1),?-SMA,E-Cadherin in renal proximal tubular epithelial cells(HKCs)and role of AG490,an antagonist of Janus kinase.Methods Cultured HKCs cells were divided into four groupslow glucose group(LG),high glucose group(HG),high mannitol group(LG+M),and HG+AG490 group(AG).Immunoprecipitation and Western blot analysis were used to measure the expressions of tryosine phosphorylated Janus kinase 2(p-JAK2),STAT1,STAT3,p-STAT1,p-STAT3 and ?-SMA,E-Cadherin.The contents of TGF-?1 and type I collagen in the supernatants of the cultured HKCs were detected by ELISA.TGF-?1 mRNA were measured by RT-PCR.ResultsCompared with low glucose control group,the expressions of JAK2,p-STAT1,p-STAT3 and TGF-?1 mRNA were significantly increased in HG group from 6 to 72 h.Meanwhile,the contents of TGF-?1 and collagen I in the supernatants and the expression of ?-SMA were increased,the expression of E-Cadherin was decreased.The expression of JAK2,p-STAT1,p-STAT3 and TGF-?1 mRNA and the level of TGF-?1,collagen I in the supernatant s in HG+AG490 group were obviously lower than those of the HG group.The expression of ?-SMA and E-Cadherinwas also decreased in HG+AG490 group.Conclusion Activation of JAK/STAT signaling pathway seems to be involved in the high glucos induced overproduction of TGF-?1 and ECM proteins in HKCs.