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

Vascular calcification (VC) is a strong predictor of cardiovascular mortality and overall mortality in patients with chronic kidney disease (CKD); however, the molecular mechanisms underlying VC have yet to be elucidated. Here, we report the role of the deubiquitinating enzyme BRCC36 in the process of VC in CKD. We established an in vitro VC model of vascular smooth muscle cells (VSMCs) and an adenine-induced CKD mouse model. The expression of BRCC36 was significantly decreased in both the in vivo and in vitro VC models. Alizarin red staining and calcium content assays showed that BRCC36 overexpression reduced calcium deposition in the presence of calcifying medium, while the contractile protein alpha-smooth muscle actin (alpha-SMA) was upregulated and phosphorylated beta-catenin was downregulated. Cell immunofluorescence showed that BRCC36 over expression also reduced the expression of phosphorylated beta-catenin in the nucleus in the presence of calcifying medium. In addition, coimmunoprecipitation showed that BRCC36 can bind to beta-catenin. These results suggest that BRCC36 can interact with beta-catenin, the main effector protein of the Wnt/beta-catenin pathway, inhibiting the phosphorylation of beta-catenin and negatively regulating the cell signalling pathway, thereby inhibiting VC. This may provide new insights into the molecular mechanisms of VC in the context of CKD.

Automated summary

This study investigated the role of the deubiquitinating enzyme BRCC36 in the process of vascular calcification (VC) in patients with chronic kidney disease (CKD). The results showed that BRCC36 can interact with beta-catenin and inhibit its phosphorylation, negatively regulating the cell signaling pathway and inhibiting VC.