Research Paper Volume 16, Issue 16 pp 11877—11892
Acyl-CoA thioesterase 13 (ACOT13) attenuates the progression of autosomal dominant polycystic kidney disease in vitro via triggering mitochondrial-related cell apoptosis
- 1 Department of Infectious Disease, The First Hospital of Jilin University, Changchun 130021, China
- 2 Department of Pathogenic Biology, School of Basic Medicine, Beihua University, Jilin 132013, China
Received: December 19, 2023 Accepted: July 5, 2024 Published: August 21, 2024
https://doi.org/10.18632/aging.206054How to Cite
Copyright: © 2024 Wang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
Purpose: Autosomal dominant polycystic kidney disease (ADPKD) is the most common cause of end-stage kidney disease. It has been shown that Acyl-CoA thioesterase 13 (ACOT13) level was reduced in renal cystic tissues from ADPKD patients. However, the role of ACOT13 in ADPKD remains largely elusive.
Methods: The data in the GSE7869 dataset were acquired from the GEO database to determine ACOT13 level between normal renal cortical tissues and renal cystic tissues. Next, the potential functions of ACOT13 were explored by gene set enrichment analysis (GSEA). Furthermore, ACOT13 level in ADPKD cells (WT9-12) was verified by RT-qPCR. The effects of ACOT13 on WT9-12 cell growth were evaluated using the EdU staining and flow cytometry assays.
Results: Compared to normal group, ACOT13 mRNA level was obviously reduced in renal cystic tissues and WT9-12 cells. Meanwhile, GSEA results showed that compared to the low ACOT13 expression group, PI3K-Akt and MAPK signaling pathways were inactivated, and PPAR signaling pathway and fatty acid metabolism were activated in high ACOT13 expression group. Furthermore, overexpression of ACOT13 notably reduced WT9-12 cell proliferation and triggered cell cycle arrest. Moreover, ACOT13 overexpression remarkably triggered apoptosis, increased cleaved caspase 3 protein level, reduced ATP production and induced loss of mitochondrial membrane potential in WT9-12 cells, suggesting that ACOT13 overexpression could trigger mitochondrial-related apoptosis in WT9-12 cells.
Conclusions: Collectively, our results showed that overexpression of ACOT13 could suppress WT9-12 cell proliferation and trigger mitochondrial-mediated cell apoptosis, suggesting that ACOT13 may exert a protective role in ADPKD.
Abbreviations
Acot: Acyl-CoA thioesterase; ACOT13: Acyl-CoA thioesterase 13; ADPKD: Autosomal dominant polycystic kidney disease; DEGs: Differential expressed genes; ESRD: End-stage renal disease; FDA: Food and Drug Administration; PKD2: Polycystic kidney disease-1.