Mannan-Binding Lectin Reduces Epithelial-Mesenchymal Transition in Pulmonary Fibrosis via Inactivating the Store-Operated Calcium Entry Machinery

Journal of Innate Immunity

Jialiang Luo¹  Yu Chen¹  Yunzhi Liu¹  Daming Zuo¹  Jianbo Zhao²  Xiao Lu³  Jia Zhou³  Ping Wang³  Zhengliang Chen³  Xianghuan Xie³  Qishan Xu⁴ 

[1] Department of Medical Laboratory, School of Laboratory Medicine and Biotechnology, Southern Medical University, Guangzhou, China;Division of Vascular and Interventional Radiology, Department of General Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, China;Guangdong Province Key Laboratory of Proteomics, Department of Immunology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China;Microbiome Medicine Center, Zhujiang Hospital, Southern Medical University, Guangzhou, China;

关键词: idiopathic pulmonary fibrosis;    mannan-binding lectin;    epithelial-mesenchymal transition;    store-operated calcium entry;    pdk1;   

DOI  :  10.1159/000524693

来源: DOAJ

【 摘 要 】

Idiopathic pulmonary fibrosis (IPF) is a type of idiopathic interstitial pneumonia with a poor clinical prognosis. Increasing evidence has demonstrated that epithelial-mesenchymal transition (EMT) contributes to the production of pathogenic myofibroblasts and plays a pivotal role in the development of pulmonary fibrosis. Mannan-binding lectin (MBL) is a soluble calcium-dependent complement molecule. Several studies have reported associations between serum MBL levels and lung diseases; however, the effect of MBL on IPF remains unknown. The present study observed aggravated pulmonary fibrosis in bleomycin-treated MBL−/− mice compared with their wild-type counterparts. Lung tissues from bleomycin-treated MBL−/− mice displayed a more severe EMT phenotype. In vitro studies determined that MBL inhibited the EMT process through attenuating store-operated calcium entry (SOCE) signaling. It was further demonstrated that MBL promoted the ubiquitination of Orai1, an essential component of SOCE, via pyruvate dehydrogenase kinase 1 (PDK1)-serum glucocorticoid-regulated kinase 1 signaling. PDK1 inhibition abolished the MBL-mediated regulation of SOCE activity and the EMT process. Notably, biochemical analysis showed that MBL interacted with PDK1 and contributed to PDK1 ubiquitination. In summary, the present findings suggested that MBL limited the EMT phenotype in human alveolar epithelial cells through regulation of SOCE, and MBL could be recognized as a potential therapeutic target for IPF.

【 授权许可】

Unknown