BRCC36 prevents vascular calcification in chronic kidney disease through the β-catenin signalling pathway

Area of Science:

• Biochemistry
• Nephrology
• Cardiovascular Biology

Background:

• Vascular calcification (VC) is a significant predictor of mortality in chronic kidney disease (CKD) patients.
• The precise molecular mechanisms driving VC in CKD remain incompletely understood.
• Identifying novel molecular targets is crucial for developing therapeutic strategies against VC.

Purpose of the Study:

• To investigate the role of the deubiquitinating enzyme BRCC36 in the pathogenesis of VC within the context of CKD.
• To elucidate the molecular interactions and signaling pathways influenced by BRCC36 in vascular smooth muscle cells (VSMCs).

Main Methods:

• Establishment of an in vitro VC model using VSMCs and an in vivo adenine-induced CKD mouse model.
• Assessment of BRCC36 expression levels in VC models.
• Evaluation of calcium deposition using Alizarin red staining and calcium content assays.
• Analysis of α-smooth muscle actin (α-SMA) and β-catenin phosphorylation via immunofluorescence and co-immunoprecipitation.

Main Results:

• BRCC36 expression was significantly decreased in both in vitro and in vivo VC models.
• Overexpression of BRCC36 markedly reduced calcium deposition in VSMCs.
• BRCC36 upregulation led to increased α-SMA and decreased phosphorylated β-catenin, particularly in the nucleus.
• Co-immunoprecipitation confirmed a direct binding interaction between BRCC36 and β-catenin.

Conclusions:

• BRCC36 plays a protective role against VC in CKD by interacting with β-catenin.
• BRCC36 inhibits VC by modulating the Wnt/β-catenin signaling pathway, specifically by reducing β-catenin phosphorylation.
• BRCC36 represents a potential therapeutic target for mitigating VC in CKD patients.