Research ArticleKidney Disease

Yin Yang 1 protein ameliorates diabetic nephropathy pathology through transcriptional repression of TGFβ1

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Science Translational Medicine  18 Sep 2019:
Vol. 11, Issue 510, eaaw2050
DOI: 10.1126/scitranslmed.aaw2050

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A target in diabetic nephropathy

Diabetic nephropathy (DN) is a major cause of kidney failure, but treatments for associated fibrosis and glomerulosclerosis are lacking. Here, Gao and Li et al. showed that Yin Yang 1 (YY1) protein negatively regulates transforming growth factor–β1 (TGFβ1) in human mesangial renal cells (HMRCs) by binding the TGFB1 promoter to repress its transcription. Overexpression and knockdown of Yy1 conversely affected DN progression in diabetic mouse models, and in humans, YY1 expression in glomeruli negatively correlated with TGFβ1 and renal fibrosis. The small molecule eudesmin increased YY1 expression in HMRCs and attenuated renal fibrosis in diabetic mice, demonstrating that YY1 is a potential antifibrotic target in DN.

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