Connectivity mapping of a chronic kidney disease progression signature identified lysine deacetylases as novel therapeutic targets

Tubulointerstitial injury is an important determinant of chronic kidney disease progression, yet treatment is limited. Accordingly, we derived a chronic kidney disease progression signature based on aging and disease in Col4a3 –/– mice, a model associated with proteinuria and progressive loss of kidney function. Computational drug repurposing with the Connectivity Map identified vorinostat, a lysine deacetylase inhibitor, as a candidate treatment to reverse progression signature gene expression. Vorinostat administrat ion significantly increased the lifespan of Col4a3–/– mice and attenuated tubulointerstitial fibrosis and JNK phosphorylation in the kidneys of Col4a3–/– mice.

Source: Kidney International - February 17, 2020 Category: Urology & Nephrology Authors: Vanessa R. Williams, Ana Konvalinka, Xuewen Song, Xiaohua Zhou, Rohan John, York Pei, James W. Scholey Tags: Basic Research Source Type: research