Long non‑coding RNA TUG1 sponges microRNA‑9 to protect podocytes from high glucose‑induced apoptosis and mitochondrial dysfunction via SIRT1 upregulation

Lei,Min; Ke,Guibao; Wang,Yan; Luo,Dan; Hu,Yao

doi:10.3892/etm.2022.11161

Long non‑coding RNA TUG1 sponges microRNA‑9 to protect podocytes from high glucose‑induced apoptosis and mitochondrial dysfunction via SIRT1 upregulation

Authors:
- Min Lei
- Guibao Ke
- Yan Wang
- Dan Luo
- Yao Hu
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Affiliations: Department of Nephrology, Affiliated Hospital and Clinical Medical College of Chengdu University, Jinniu, Chengdu, Sichuan 610081, P.R. China
Published online on: January 24, 2022 https://doi.org/10.3892/etm.2022.11161
Article Number: 236
Copyright: © Lei et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Podocyte apoptosis and mitochondrial dysfunction serve a major role in diabetic nephropathy progression. The present study revealed a molecular mechanism regulating podocyte apoptosis and mitochondrial dysfunction. In vitro models were established using conditionally immortalized mouse podocyte clonal cells treated with high glucose (HG). Reverse quantitative‑transcription PCR were used to detect gene expression, western blotting and immunofluorescence were used to detect protein expression, Cell Counting Kit‑8 was used to detect cell viability and flow cytometry was used to detect cell apoptosis. HG treatment in the mouse podocyte clonal cells downregulated taurine‑upregulated gene 1 (TUG1) expression and decreased viability in a dose‑dependent manner. In addition, TUG1 knockdown (KD) increased HG‑induced apoptosis, while TUG1 overexpression (OE) reduced HG‑induced apoptosis in podocytes. HG‑induced mitochondrial dysfunction was identified in podocytes, with increased reactive oxygen species levels, decreased complex I/III activity and decreased basal/maximal oxygen consumption rate. TUG1 KD worsened HG‑induced mitochondrial dysfunction, and TUG1 OE reversed these effects. At the molecular level, TUG1 was revealed to promote sirtuin 1 (SIRT1) expression by sponging microRNA (miR)‑9, and SIRT1 OE reversed the HG‑induced apoptosis and mitochondrial dysfunction increased by TUG1 KD. The present data indicated that downregulation of TUG1 induced by HG was associated with HG‑induced apoptosis and mitochondrial dysfunction in podocytes, and that TUG1 protected HG‑induced podocytes by promoting SIRT1 expression via miR‑9 inhibition.

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