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BRCC36 regulates β-catenin ubiquitination to alleviate vascular calcification in chronic kidney disease

Yalan Li1, Xiaoyue Chen1, Yiqing Xiong1

  • 1Department of Nephrology, Jiangsu Province Hospital, The First Affiliated Hospital of Nanjing Medical University, Nanjing, #300 Guangzhou Road, 210029, China.

Journal of Translational Medicine
|September 3, 2024
PubMed

Insights

BRCA1/BRCA2-containing complex subunit 36 (BRCC36) protects against vascular calcification (VC) in chronic kidney disease (CKD) by inhibiting the Wnt/β-catenin pathway. Upregulating BRCC36 may offer a novel therapeutic strategy for VC in CKD patients.

Area of Science:

  • Cardiovascular Biology
  • Nephrology
  • Molecular Biology

Background:

  • Vascular calcification (VC) is prevalent in chronic kidney disease (CKD) with no effective pharmaceutical treatments.
  • BRCA1/BRCA2-containing complex subunit 36 (BRCC36) is linked to osteoblast differentiation, but its role in VC is unclear.

Purpose of the Study:

  • To investigate the role and mechanisms of BRCC36 in the development of VC.

Main Methods:

  • Examined BRCC36 expression in human and mouse CKD models and vascular smooth muscle cells (VSMCs).
  • Utilized gain- and loss-of-function experiments, Western blotting, qPCR, immunofluorescence, immunohistochemistry, coimmunoprecipitation, and TOPFlash luciferase assays.
  • Investigated the regulation of the Wnt/β-catenin pathway by BRCC36.

Main Results:

  • BRCC36 expression was reduced in calcified arteries and VSMCs from CKD patients and mice.
  • BRCC36 overexpression alleviated VC, while depletion worsened it, inhibiting VSMC osteogenic differentiation.
  • BRCC36 inhibited the Wnt/β-catenin pathway by reducing β-catenin ubiquitination; pioglitazone increased BRCC36 and attenuated VC.

Conclusions:

  • The BRCC36-β-catenin axis is crucial in VC pathogenesis.
  • BRCC36 and β-catenin represent potential therapeutic targets for preventing VC in CKD.
Abstract

Keywords:
BRCC36Chronic kidney diseaseUbiquitin‒proteasome degradationVascular calcificationβ-catenin

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