Pioglitazone attenuates kidney fibrosis via miR-21-5p modulation.
Pioglitazone attenuates kidney fibrosis via miR-21-5p modulation.
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发表时间:
2019
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通讯作者:
Yao Li
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作者:
Sun Li;Xu Tianhua;Chen Ying;Qu Wei;Sun Dan;Song Xiaoyu;Yuan Quan;Yao Li
Pioglitazone has been demonstrated to exert anti-fibrotic and renoprotective effects. But the detailed pharmacological mechanisms have not been clearly revealed. The present study aimed to investigate the possible mechanisms of pioglitazone in these two effects. TGF-β1-stimulated HK-2 cells and unilateral ureteral obstruction.(UUO) mice were used as in vitro and in vivo models. The results showed that pioglitazone inhibited Smad-2/3.phosphorylation, upregulated Smad-7 expression and downregulated miR-21-5p expression in TGF-β1-exposed.HK-2 cells. In addition, miR-21-5p inhibitors replicated the anti-fibrotic effects of pioglitazone, and miR-21-5p.mimics inhibited these effects. In in vivo study, pioglitazone attenuated UUO-induced renal fibrosis and significantly decreased the expressions of pro-fibrotic proteins. Whereas, agomir of miR-21-5p inhibited the renoprotective function of pioglitazone in UUO mice. In conclusion, the present data suggest that modulation of.miR-21-5p/Smad-7 signal may be involved in the anti-fibrotic effect of pioglitazone in the kidney of UUO mice.