Pediatrics Department, The People's Hospital of Jiulongpo District, Chongqing, China.
Autoimmunity. 2023 Dec;56(1):2281223. doi: 10.1080/08916934.2023.2281223. Epub 2023 Nov 15.
Airway remodeling is an important pathologic factor in the progression of asthma. Abnormal proliferation and migration of airway smooth muscle cells (ASMCs) are important pathologic mechanisms in severe asthma. In the current study, claudin-1 (CLDN1) was identified as an asthma-related gene and was upregulated in ASMCs stimulated with platelet-derived growth factor BB (PDGF-BB). Cell counting kit-8 and EdU assays were used to evaluate cell proliferation, and transwell assay was carried out to analyze cell migration and invasion. The levels of inflammatory factors were detected using enzyme-linked immunosorbent assay. The results showed that CLDN1 knockdown inhibited the proliferation, migration, invasion, and inflammation of ASMCs treated with PDGF-BB, whereas overexpression of CLDN1 exhibited the opposite effects. Protein-protein interaction assay and co-immunoprecipitation revealed that CLDN1 directly interacted with matrix metalloproteinase 14 (MMP14). CLDN1 positively regulated MMP14 expression in asthma, and MMP14 overexpression reversed cell proliferation, migration, invasion, and inflammation induced by silenced CLDN1. Taken together, CLDN1 promotes PDGF-BB-induced cell proliferation, migration, invasion, and inflammatory responses of ASMCs by upregulating MMP14 expression, suggesting a potential role for CLDN1 in airway remodeling in asthma.
气道重塑是哮喘进展的一个重要病理因素。气道平滑肌细胞（ASMCs）的异常增殖和迁移是重症哮喘的重要病理机制。在本研究中，Claudin-1（CLDN1）被鉴定为与哮喘相关的基因，在血小板衍生生长因子 BB（PDGF-BB）刺激的 ASMCs 中上调。细胞计数试剂盒-8 和 EdU 检测用于评估细胞增殖，transwell 检测用于分析细胞迁移和侵袭。酶联免疫吸附试验检测炎症因子水平。结果表明，CLDN1 敲低抑制了 PDGF-BB 处理的 ASMCs 的增殖、迁移、侵袭和炎症，而过表达 CLDN1 则表现出相反的效果。蛋白质-蛋白质相互作用测定和共免疫沉淀显示 CLDN1 与基质金属蛋白酶 14（MMP14）直接相互作用。CLDN1 正向调节哮喘中 MMP14 的表达，而过表达 MMP14 逆转了沉默 CLDN1 诱导的细胞增殖、迁移、侵袭和炎症。总之，CLDN1 通过上调 MMP14 的表达促进 PDGF-BB 诱导的 ASMCs 增殖、迁移、侵袭和炎症反应，提示 CLDN1 在哮喘气道重塑中可能具有重要作用。
