LncRNA TUG1 ameliorates diabetic nephropathy by inhibiting miR-21 to promote TIMP3-expression.

Diabetic nephropathy (DN) is one of the most important microvascular diseases in diabetic patients and has been the first cause of end stage renal disease (ESRD). In this study, we are aims to investigate the genetic mechanisms of lncRNA in the regulation of DN renal fibrosis. First, we have found that the expression of lncRNA TUG1 in db/db DN mice kidney tissue and high glucose-stimulated NRK-52E cells were down-regulated and the overexpression of lncRNA TUG1 could inhibit cell fibrosis of high glucose-stimulated of NRK-52E. Second, online software program Starbase predicts that miR-21 is a target gene of lncRNA TUG1 and TIMP3 is the target gene of miR-21, which have been verified by luciferase reporter assay and RNA Binding Protein Immunoprecipitation (RIP). Last, the renal fibrosis in DN mice and cell fibrosis in high glucose-stimulated NRK-52E cells were also evaluated. We have proven that overexpression of lncRNA TUG1 can promote the expression of TIMP3 through targeting the miR-21, thereby inhibiting cell fibrosis in high glucose-stimulated NRK-52E cells and renal fibrosis in DN mice. Our results indicated that lncRNA TUG1 could indirectly regulated the expression of TIMP3 by targeting miR-21. LncRNA TUG1 inhibited high glucose-stimulated NRK-52E cell fibrosis and renal fibrosis in DN mice, which provides a theoretical basis for the treatment of DN fibrosis. IJCEP