Details

Autor(en) / Beteiligte

• Liang, Shixiu
• Zhou, Zicong
• Zhou, Zili
• Liang, Jiayuan
• Lin, Weixian
• Zhang, Changyun
• Zhou, Chi
• Zhao, Haijin
• Meng, Xiaojing
• Zou, Fei
• Yu, Changhui
• Cai, Shaoxi

Titel

Blockade of CBX4-mediated β-catenin SUMOylation attenuates airway epithelial barrier dysfunction in asthma

Ist Teil von

• International immunopharmacology, 2022-12, Vol.113, p.109333, Article 109333

Ort / Verlag

Elsevier B.V

Erscheinungsjahr

2022

Link zum Volltext

Quelle

ScienceDirect

Beschreibungen/Notizen

• [Display omitted] •Epithelial barrier dysfunction is involved in the pathogenesis of asthma.•Inhibition of SUMOylation attenuates house dust mite (HDM)-induced epithelial barrier dysfunction.•Inhibition of β-catenin SUMOylation promotes its membrane localization and represses Wnt/β-catenin signaling.•β-catenin SUMOylation is mediated by CBX4 and knockdown of CBX4 significantly attenuates HDM-induced epithelial barrier dysfunction and allergic airway inflammation. 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 determined by co-immunoprecipitation (CO-IP) and proximity ligation assay (PLA). HDM treatment significantly enhanced SUMOylation levels of β-catenin, while no effect was seen on ZO-1, Occludin, and E-cadherin SUMOylation levels. Inhibition of β-catenin SUMOylation through 2-D08 treatment or SUMOylation modification site mutant (K233A) promoted its membrane localization and repressed Wnt/β-catenin signaling. Further, we identified that CBX4, an E3 ligase, mediated SUMOylation of β-catenin. Knockdown of CBX4 promoted β-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 β-catenin SUMOylation by targeting CBX4 mitigated HDM-induced epithelial barrier dysfunction in asthma.