Butyrate alleviates diabetic kidney disease by mediating the miR-7a-5p/P311/TGF-β1 pathway

Abstract

It has been reported that butyrate played an protect role in diabetic kidney disease (DKD) while the mechanism was still not clear. Transforming growth factor-β1 (TGF-β1) is the initial factor which triggers the profibrotic signaling cascades. P311 is an RNA-binding protein, which could stimulate TGF-β1 translation in several cell types. In our study, we found that supplementary of butyrate alleviated fibrosis and suppressed the expression of TGF-β1 and P311 in the kidney of db/db mice as well as high glucose (HG)-induced SV40-MES-13 cells. Overexpression of P311 offset the inhibition of butyrate on TGF-β1 in SV40-MES-13 cells. To make clear the mechanism of butyrate in regulating P311, microRNAs (miRNAs) of the SV40-MES-13 cells were sequenced. We found that miR-7a-5p was significantly decreased in the HG-induced SV40-MES-13 cells and the kidney of db/db mice, while giving butyrate reversed this change. Besides, miR-7a-5p could specifically target the 3' UTR of P311's mRNA and suppressed the expression of P311 in the SV40-MES-13 cells. Giving miR-7a-5p inhibitor blocked the inhibition of butyrate on P311 and TGF-β1. Introducing the miR-7a-5p agomir into db/db mice alleviated renal fibrosis and inhibit the expression of P311 and TGF-β1. In conclusion, butyrate alleviated DKD by mediating the miR-7a-5p/P311/TGF-β1 pathway.

Keywords: SV40-MES-13 cells; butyrate; db/db mice; diabetic kidney disease; fibrosis.