Blockade of CBX4-mediated β-catenin SUMOylation attenuates airway epithelial barrier dysfunction in asthma
Blockade of CBX4-mediated β-catenin SUMOylation attenuates airway epithelial barrier dysfunction in asthma
复制标题
阻断 CBX4 介导的 β-连环蛋白 SUMOylation 可减轻哮喘气道上皮屏障功能障碍
DOI：
10.1016/j.intimp.2022.109333
复制
发表时间：
2022-10-25
影响因子：
5.6
通讯作者：
Cai, Shaoxi
中科院分区：
文献类型：
--
作者：
Liang, Shixiu;Zhou, Zicong;Cai, Shaoxi
Epithelial barrier dysfunction is involved in the pathogenesis of asthma. Previous studies show that SUMOylation can regulate epithelial junction molecule localization. However, the role of SUMOylation in epithelial barrier dysfunction in asthma remains unclear. This study found that inhibition of SUMOylation attenuates house dust mite (HDM)-induced epithelial barrier dysfunction. The SUMOylation levels of junction molecules were deter-mined by co-immunoprecipitation (CO-IP) and proximity ligation assay (PLA). HDM treatment significantly enhanced SUMOylation levels of beta-catenin, while no effect was seen on ZO-1, Occludin, and E-cadherin SUMOylation levels. Inhibition of beta-catenin SUMOylation through 2-D08 treatment or SUMOylation modification site mutant (K233A) promoted its membrane localization and repressed Wnt/beta-catenin signaling. Further, we identified that CBX4, an E3 ligase, mediated SUMOylation of beta-catenin. Knockdown of CBX4 promoted beta-catenin membrane localization and improved epithelial barrier function. In vivo analysis showed that AAV6-shCBX4-mediated knockdown of CBX4 attenuated HDM-induced allergic airway inflammation and epithelial barrier dysfunction. The findings showed that inhibiting beta-catenin SUMOylation by targeting CBX4 mitigated HDM-induced epithelial barrier dysfunction in asthma.
