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, f...
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doaj-d957f529dfa246f88422cbab5a027aeb2021-08-29T11:46:19ZengBMCBMC Nephrology1471-23692021-08-0122111310.1186/s12882-021-02473-0Long non-coding RNA TUG1 knockdown promotes autophagy and improves acute renal injury in ischemia-reperfusion-treated rats by binding to microRNA-29 to silence PTENZhiquan Xu0Xiaoyan Huang1Qiuyu Lin2Wei Xiang3Department of Nephrology, Rheumatology and Immunology, Hainan Women and Children’s Medical CenterDepartment of Genetics, Metabolism and Endocrinology, Hainan Women and Children’s Medical CenterDepartment of Respiratory, Hainan Maternal and Children’s Medical CenterDepartment of Pediatrics, Hainan Maternal and Children’s Medical CenterAbstract 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.https://doi.org/10.1186/s12882-021-02473-0Renal ischemia-reperfusionAutophagyApoptosisLong noncoding RNA TUG1PTENmcroRNA-29 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Zhiquan Xu Xiaoyan Huang Qiuyu Lin Wei Xiang |
spellingShingle |
Zhiquan Xu Xiaoyan Huang Qiuyu Lin Wei Xiang 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 BMC Nephrology Renal ischemia-reperfusion Autophagy Apoptosis Long noncoding RNA TUG1 PTEN mcroRNA-29 |
author_facet |
Zhiquan Xu Xiaoyan Huang Qiuyu Lin Wei Xiang |
author_sort |
Zhiquan Xu |
title |
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 |
title_short |
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 |
title_full |
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 |
title_fullStr |
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 |
title_full_unstemmed |
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 |
title_sort |
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 |
publisher |
BMC |
series |
BMC Nephrology |
issn |
1471-2369 |
publishDate |
2021-08-01 |
description |
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. |
topic |
Renal ischemia-reperfusion Autophagy Apoptosis Long noncoding RNA TUG1 PTEN mcroRNA-29 |
url |
https://doi.org/10.1186/s12882-021-02473-0 |
work_keys_str_mv |
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