miR-21 promotes renal fibrosis in diabetic nephropathy by targeting PTEN and SMAD7
Aaron D McClelland, Michal Herman-Edelstein, Radko Komers, Jay C Jha, Catherine E Winbanks, Shinji Hagiwara, Paul Gregorevic, Phillip Kantharidis, Mark E Cooper
CLINICAL SCIENCE | PORTLAND PRESS LTD | Published : 2015
The cytokine transforming growth factor (TGF)-β1 plays a central role in diabetic nephropathy (DN) with data implicating the miRNA (miR) miR-21 as a key modulator of its prosclerotic actions. In the present study, we demonstrate data indicating that miR-21 up-regulation positively correlates with the severity of fibrosis and rate of decline in renal function in human DN. Furthermore, concomitant analyses of various models of fibrotic renal disease and experimental DN, confirm tubular miR-21 up-regulation. The fibrotic changes associated with increased miR-21 levels are proposed to include the regulation of TGF-β1-mediated mothers against decapentaplegic homolog 3 (SMAD3)- and phosphoinositid..View full abstract
Awarded by Heart Foundation
Awarded by National Health and Research Council of Australia
This work was supported by the Heart Foundation [grant number G11M 6134]; the Diabetes Australia Research Trust; the Skip Martin Award; the Vera Dalgleish Phillips Fellowship (to P.K.); the National Health and Research Council of Australia [grant number 106448 (to M.E.C.)]; and the Victorian Government's Operational Infrastructure Support (OIS) Program.