Long non-coding RNA TUG1 knockdown promotes autophagy and improves acute renal injury in ischemia-reperfusion-treated rats by binding to microRNA-29 to silence PTEN

Abstract

Objective Long noncoding RNA (lncRNA) taurine upregulated gene 1 (TUG1) is increased under the condition of ischemia. This study intended to identify the mechanism of TUG1 in renal ischemia-reperfusion (I/R). Methods First, a rat model of acute renal injury induced by I/R was established, followed by the measurement of blood urea nitrogen (BUN), serum creatine (SCr), methylenedioxyphetamine (MDA) and superoxide dismutase (SOD) in the serum of rats. TUG1 was knocked down in I/R rats (ko-TUG1 group). Next, histological staining was used to evaluate the pathological damage and apoptosis of rat kidney. Western blot analysis was used to detect the levels of apoptosis- and autophagy-related proteins and transmission electron microscope was used to observe autophagosomes. Autophagy and apoptosis were evaluated after inhibition of the autophagy pathway using the inhibitor 3-MA. The targeting relation among TUG1, microRNA (miR)-29 and phosphatase and tensin homolog (PTEN) were validated. Lastly, the effects of TUG1 on biological behaviors of renal tubular cells were evaluated in vitro. Results In vivo, the levels of BUN, SCr and MDA in the serum of I/R-treated rats were increased while 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 all reversed in rats in the ko-TUG1 group. Autophagy inhibition (ko-TUG1 + 3-MA group) averted the protective effect of TUG1 knockdown on I/R-treated rats. TUG1 could competitively bind to miR-29 to promote PTEN expression. In vitro, silencing TUG1 (sh-TUG1 group) promoted viability and autophagy of renal tubular cells and inhibited apoptosis. Conclusions LncRNA TUG can promote PTEN expression by competitively binding to miR-29 to promote autophagy and inhibited apoptosis, thus aggravating acute renal injury in I/R-treated rats.

Klotho-derived peptide 1 inhibits cellular senescence in the fibrotic kidney by restoring Klotho expression via posttranscriptional regulation

“…In this study, we show that lncRNA-TUG1 is down-regulated in CKD, functions as miR-223-3p sponge by binding to its complementary site, and diminishes miR-223-3p-mediated Klotho suppression. Such sponge function of lncRNA-TUG1 is supported by earlier reports that several miRNAs including miR-145-5p 50 , miR-144-3p 53 , miR-29 58 can also bind to lncRNA-TUG1. The fact that lncRNA-TUG1 and miR-223-3p reciprocally antagonize each other underscores that they could form a double-negative feedback loop (Figure 8 k), which amplifies the capacity of miR-223-3p in suppressing Klotho expression.…”

Research hotspots and development trends of microRNA in ischemia-reperfusion: network analysis of academic journals oriented by bibliometric and visualization

“…LncRNA HOTAIR regulates autophagy in liver IR injury through miR-20b ( 18 ). LncRNA TUG can promote PTEN expression, autophagy, and apoptosis by competitively combining miR-29, thereby aggravating acute renal injury in rats treated with ischemia-perfusion ( 19 ). LncRNA C2dat2 promotes autophagy and apoptosis in cerebral IR injury through the miR-30d-5p/DDIT4/mTOR axis ( 20 ).…”