Total Glucosides of Paeony Inhibited Autophagy and Improved Acute Kidney Injury Induced by Ischemia-Reperfusion via the lncRNA TUG1/miR-29a/PTEN Axis

Abstract

Objective

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

Data Sharing Statement

All the data generated or analyzed during this study are included in this published article.

Disclosure

The authors declare that they have no competing interests.

Additional information

Funding

This work was partially supported by the National Natural Science Foundation of China Youth Program (Grant No. 81700606). The funding body did not participate in the design of the study and collection, analysis, and interpretation of data and in writing the manuscript.