Leukemia inhibitory factor attenuates renal fibrosis through Stat3-miR-29c

摘要

Leukemia inhibitory factory (LIF), as a member of the IL-6 family, has been reported to ameliorate myocardial fibrosis and myocardial cell death. The purpose of the present study was to investigate the effect of LIF on renal fibrosis and its underlying mechanism. Our results showed, first, that LIF inhibited collagen type 1 and collagen type 3 expression induced by ANG II in NRK-49F (rat kidney fibroblast) cells and in mice with unilateral ureteral obstruction. Second, LIF induced Stat3 Tyr705 phosphorylation and inhibited Stat3 Tyr705 and Ser727 phosphorylation induced by ANG II in NRK-49F cells. Third, LIF exerted an antirenal fibrosis effect mainly through activation of Stat3 Tyr705 phosphorylation in NRK-49F cells. These effects of LIF were not observed in StatS"'" cells. Finally, LIF-Stat3 upregulated microRNA-29c expression, and the latter down-regulated collagen type 1 and collagen type 3 expression in NRK-49F cells and in mice with unilateral ureteral obstruction. In conclusion, LIF played a role in antirenal fibrosis by competitively activating Stat3 Tyr705 phosphorylation, which upregulated microRNA-29c to suppress collagen expression.