Objective: To observe the effect of Klotho on high glucose-activated phosphorylation of signal transducer and activator of transcription 3 (STAT3) and expression of fibrosis related gene in renal tubular epithelial cells under high glucose. Methods: Human proximal tubular epithelial cells (HK2) were cultured and incubated with high glucose (HG, D-glucose 30 mmol/L), normal glucose (NG, D-glucose 5 mmol/L), high mannitol (HM, D-glucose 5 mmol/L and mannitol 25 mmol/L), and Klotho or HO3867 in the presence of high glucose. STAT3 activation and expression of target genes were assayed by Western blot or real time fluorescence quantitative PCR(rt-fqPCR). Results: Compared with NG or HM, a significant decrease of endogenous Klotho gene level was detected after HG treatment(P<0.01). Western blot analysis revealed that the level of STAT3 phosphorylation was significantly increased after HG treatment compared with NG or HM(P<0.01). The activation of STAT3 induced by high glucose was markedly reduced by Klotho or HO3867 treatment(P<0.01). The level of mRNA expression of fibrosis related gene(α-SMA, Col4A1, FN) was significantly increased after high glucose treatment in HK-2 cells (P<0.01), while was markedly inhibited by Klotho treatment(P<0.01). HO3867, the inhibitor of STAT3, partially decreased the mRNA levels of above mentioned genes (P<0.01). Conclusions: Soluble Klotho could attenuate high glucose-induced renal fibrosis, which might be achieved partially through inhibition of STAT3 pathway.
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