Drug Design, Development and Therapy (May 2021)
Total Glucosides of Paeony Inhibited Autophagy and Improved Acute Kidney Injury Induced by Ischemia-Reperfusion via the lncRNA TUG1/miR-29a/PTEN Axis
Abstract
Xiaoyan Chang,1 Pei Zhang,1 Xing-Xin Xu,1 Bo Pang2 1Department of Nephropathy, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, People’s Republic of China; 2Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, People’s Republic of ChinaCorrespondence: Bo PangThe First Affiliated Hospital of Anhui Medical University, No. 218 Jixi Road, Shushan District, Hefei, 230022, Anhui, People’s Republic of ChinaTel +86 0551-62922913Email [email protected]: Total glucosides of paeony (TGP) has been proven to affect anti-inflammatory, immunomodulatory and hypoxia tolerance. This study investigates the effect of TGP on autophagy in acute kidney injury (AKI) induced by ischemia-reperfusion (I/R).Methods: Rat model of AKI induced by I/R was established. Rats were administered with TGP at different doses by oral gavage. The contents of BUN, creatinine, NGAL, Kim-1 and IL-18 were detected. The levels of inflammatory factors (TNF-α, IL-1β and IL-6) and autophagy were measured. The expressions of lncRNA TUG1, miR-29a and PTEN were detected and their binding relationships were verified. I/R rat model with overexpressed TUG1 was established to explore the effect of TGP on kidney injury and autophagy. The hypoxia/reoxygenation (HR) model of HK-2 cells and the HR model of HK-2 cells overexpressing TUG1 and low-expressing PTEN were established.Results: TGP decreased the contents of BUN, creatinine, NGAL, Kim-1 and IL-18, and reduced the levels of inflammatory factors. LncRNA TUG1 and PTEN were downregulated, and miR-29a was upregulated in kidney tissues. The binding relationships between lncRNA TUG1 and miR-29a, and miR-29a and PTEN were confirmed. TGP suppressed PTEN expression via the lncRNA TUG1/miR-29a axis. Overexpressing lncRNA TUG1 attenuated the protective effect of TGP on AKI and autophagy in HK-2 cells. TGP improved cell viability and inhibited the autophagy in HR model of HK-2 cells via lncRNA TUG1/miR-29a/PTEN axis.Conclusion: TGP inhibited autophagy and improved AKI induced by I/R via the lncRNA TUG1/miR-29a/PTEN axis.Keywords: total glucosides of paeony, lncRNA TUG1/miR-29a/PTEN, ischemia-reperfusion, acute kidney injury, autophagy
