Long non-coding RNA TUG1/microRNA-29/PTEN axis in ischemia-reperfusion in a rat model

Abstract

Objective: Long non-coding RNA (lncRNA) taurine upregulated gene 1 (TUG1) is increased under ischemia. This study intended to identify the potential competing endogenous RNA network involving TUG1 in renal ischemia-reperfusion (I/R).Methods: A rat model of acute renal injury induced by I/R was established, and the differentially expressed genes were analyzed by microarray. The levels of blood urea nitrogen (BUN), serum creatine (SCr), methylenedioxyphetamine (MDA) and superoxide dismutase (SOD) in serum of rats were measured. HE staining evaluated the pathological damage of renal tissues, western blot analysis detect the levels of apoptosis- and autophagy-related proteins, immunofluorescence staining detected LC3 fluorescence intensity, and transmission electron microscope observed autophagosomes. Pull-down assay and dual luciferase reporter gene assay were used to verify the targeting relationship among TUG1, miR-29 and PTEN. The effects of TUG1 on biological behaviors of renal tubular cells were evaluated by simulating the acute renal injury induced by I/R in vitro.Results: In vivo, the levels of BUN, SCr and MDA in serum of I/R-treated rats were increased, SOD level and autophagosomes were reduced, tubule epithelial cells were necrotic, and TUG1 was upregulated in renal tissues of I/R-treated rats, which were reversed by TUG1 knockdown. Autophagy inhibition attenuated the protective effect of TUG1 knockdown on I/R-treated rats. TUG1 could competitively bind to miR-29 to promote PTEN expression. In vitro, low expression of TUG1 promoted proliferation and autophagy of renal tubular cells and inhibited apoptosis.Conclusion: TUG1 knockdown promotes autophagy and improves acute renal injury in I/R-treated rats by binding to miR-29 to silence PTEN.