2. Academic Validation
  3. miR-124-3p improves mitochondrial function of renal tubular epithelial cells in db/db mice

miR-124-3p improves mitochondrial function of renal tubular epithelial cells in db/db mice

  • FASEB J. 2023 Mar;37(3):e22794. doi: 10.1096/fj.202201202RR.
Luqun Liang 1 2,  Chunxin Wo 3,  Yao Yuan 4,  Hongjuan Cao 4,  Wanlin Tan 1 2,  Xingcheng Zhou 1 2,  Dan Wang 1 2,  Rongyu Chen 1 2,  Mingjun Shi 1 2,  Fan Zhang 1 2,  Ying Xiao 1 2,  Lingling Liu 1 2,  Yuxia Zhou 1 2,  Tian Zhang 1 2,  Yuanyuan Wang 1 5,  Bing Guo 1 6
Affiliations

Affiliations

  • 1 Department of Pathophysiology, Basic Medical College, Guizhou Medical University, Guiyang, China.
  • 2 Guizhou Provincial Key Laboratory of Pathogenesis and Drug Research on Common Chronic Diseases, Guizhou Medical University, Guiyang, China.
  • 3 Department of Pain, Affiliated Hospital of Guizhou Medical University, Guizhou Medical University, Guiyang, China.
  • 4 Clinical Medical Imaging, Guizhou Medical University, Guiyang, China.
  • 5 Guizhou Province Innovation Base of Common Major Chronic Disease Pathogenesis and Drug Development and Application, Guizhou Medical University, Guiyang, China.
  • 6 International Scientific and Technological Cooperation Base of Pathogenesis and Drug Research on Common Major Diseases, Guizhou Medical University, Guiyang, China.
PMID: 36753399 DOI: 10.1096/fj.202201202RR
Abstract

Diabetic kidney disease (DKD) is one of the most serious complications of diabetes mellitus (DM) and the main cause of end-stage renal failure. However, the pathogenesis of DKD is complicated. In this study, we found that miR-124-3p plays a key role in regulating renal mitochondrial function and explored its possible mechanism in DKD progression by performing a series of in vitro and in vivo experiments. Decreased expression of miR-124-3p was found in db/db mice compared to db/m mice. Moreover, miR-124-3p down-regulated FOXQ1 by targeting FOXQ1 mRNA 3'-UTR in NRK-52E cells. Also, an increase in FOXQ1 and down-regulation of Sirt4 were found in db/db mouse kidney and renal tubular epithelial cells cultured with high glucose and high lipid. Overexpression of FOXQ1 could further down-regulate the expression of Sirt4 and aggravate the damage of mitochondria. Conversely, the knockdown of the FOXQ1 gene induced Sirt4 expression and partially restored mitochondrial function. To verify the effects of miR-124-3p on Sirt4 and mitochondria, we found that miR-124-3p mimics could up-regulate Sirt4 and inhibit ROS production and MitoSOX, thus restoring the number and morphology of mitochondria. These results showed that under high-glucose and high-lipid conditions, the down-regulation of miR-124-3p induces FOXQ1 in renal tubular epithelial cells, which in turn suppresses Sirt4 and leads to mitochondrial dysfunction, promoting the development of DKD.

Keywords

FOXQ1; Sirt4; db/db mice; diabetic kidney disease; miR-124-3p; mitochondrial dysfunction; oxidative stress.

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