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  3. CDC20 inhibition alleviates fibrotic response of renal tubular epithelial cells and fibroblasts by regulating nuclear translocation of β-catenin

CDC20 inhibition alleviates fibrotic response of renal tubular epithelial cells and fibroblasts by regulating nuclear translocation of β-catenin

  • Biochim Biophys Acta Mol Basis Dis. 2023 Feb 9;1869(4):166663. doi: 10.1016/j.bbadis.2023.166663.
Jia He 1,  Shuang Xu 1,  Mingzhu Jiang 1,  Ting Wang 1,  Yue Zhang 1,  Zhanjun Jia 2,  Mi Bai 3,  Aihua Zhang 4
Affiliations

Affiliations

  • 1 Department of Nephrology, State Key Laboratory of Reproductive Medicine, Children's Hospital of Nanjing Medical University, Nanjing 211166, China; Jiangsu Key Laboratory of Pediatrics, Nanjing Medical University, Nanjing 210029, China.
  • 2 Department of Nephrology, State Key Laboratory of Reproductive Medicine, Children's Hospital of Nanjing Medical University, Nanjing 211166, China; Jiangsu Key Laboratory of Pediatrics, Nanjing Medical University, Nanjing 210029, China; Nanjing Key Laboratory of Pediatrics, Children's Hospital of Nanjing Medical University, Nanjing 210008, China. Electronic address: jiazj72@hotmail.com.
  • 3 Department of Nephrology, State Key Laboratory of Reproductive Medicine, Children's Hospital of Nanjing Medical University, Nanjing 211166, China; Jiangsu Key Laboratory of Pediatrics, Nanjing Medical University, Nanjing 210029, China; Nanjing Key Laboratory of Pediatrics, Children's Hospital of Nanjing Medical University, Nanjing 210008, China. Electronic address: baimi3@njmu.edu.cn.
  • 4 Department of Nephrology, State Key Laboratory of Reproductive Medicine, Children's Hospital of Nanjing Medical University, Nanjing 211166, China; Jiangsu Key Laboratory of Pediatrics, Nanjing Medical University, Nanjing 210029, China; Nanjing Key Laboratory of Pediatrics, Children's Hospital of Nanjing Medical University, Nanjing 210008, China. Electronic address: zhaihua@njmu.edu.cn.
PMID: 36764621 DOI: 10.1016/j.bbadis.2023.166663
Abstract

Fibrosis is a common pathological phenomenon in progressive kidney disease leading to eventual loss of kidney function. Previous studies demonstrated that CDC20 plays a role in cancers by regulating epithelial-mesenchymal transition (EMT) and the infiltration of fibroblasts, suggesting the potential of CDC20 in regulating fibrotic response. However, the role of CDC20 in renal fibrosis is yet unclear. Herein, we reported that renal CDC20 was remarkably upregulated in renal tubular epithelial cells and fibroblasts in chronic kidney disease (CKD) patients, which was in line with a positive correlation with the severity of kidney fibrosis. In mice with unilateral urinary obstruction, CDC20 was also strikingly enhanced, and treatment with Apcin, an inhibitor of CDC20, ameliorated kidney fibrosis. Consistently, the pharmacological inhibition of CDC20 in mouse proximal tubular epithelial cells and rat fibroblasts attenuated TGF-β1-induced fibrotic responses, while overexpression of CDC20 aggravated such responses. Additional studies revealed that CDC20 induces nuclear translocation of β-catenin, which in turn initiates and promotes the pathological process of fibrosis in CKD. Thus, enhanced CDC20 in renal tubular cells and fibroblasts promotes renal fibrosis by activating β-catenin, and CDC20 inhibition may serve as a promising strategy for the prevention and treatment of renal fibrosis.

Keywords

CDC20; Fibroblasts; Renal fibrosis; Tubular epithelial cells; β-Catenin.

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  • HY-110287
    99.71%, APC/C Inhibitor
    APC
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