Xiong Li, Liang Li-Mei, Ye Shu-Yi, Cui Xiao-Lin, Hu Shi-He, Lian Chen-Yue, Sun Wen-Jia, Lv Yang-Ping, Zhang He-De, Wang Meng, Xiang Fei, Xiong Liang, Ye Hong, Ma Wan-Li, Song Lin-Jie
Department of Respiratory and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
Key Laboratory of Respiratory Diseases of National Health Commission of China, Wuhan 430030, China.
Biomedicines. 2025 Jun 27;13(7):1581. doi: 10.3390/biomedicines13071581.
: Rheumatoid arthritis-related interstitial lung disease (RA-ILD) is a significant complication of RA which lacks effective treatments with high mortality. This study aimed to investigate the role of matrix metalloproteinase-7 (MMP-7) in mediating RA-ILD. : Based on the database of RA-ILD patients, a bioinformatics analysis was performed. A protein-protein interaction (PPI) network focusing on MMP-7 was simulated. Pleural mesothelial cells (PMCs) were treated with RA-ILD patients' serum or RA-ILD-related inflammatory factors, and the protein expressions of collagen-I and MMP-7 were examined. An arthritis model was established using complete Freund's adjuvant (CFA). Changes in the weight and joints of mice were recorded, and lung tissues were evaluated by Masson staining and Sirius red stain techniques. MMP-7 inhibitor, MMP-7 siRNA and MMP shRNA lentivirus were used to inhibit MMP-7 and investigate changes in collagen-I and fibrosis in vivo and in vitro. : MMP-7 was found to be significantly expressed in RA-ILD lung tissue by bioinformatics analysis, and MMP-7 to maybe interact with collagen-I. In vitro experiments indicated cytokines IL-1β, IL-6 and TNF-α promoted MMP-7 and collagen-I expression in PMCs. Serum obtained from patients with RA-ILD also upregulated MMP-7 and collagen-I expression in PMCs. Inhibition of MMP-7 with MMP-7 siRNA or MMP inhibitor prevented collagen-I synthesis in PMCs. In vivo, CFA induced arthritis and subpleural lung inflammation in rats, but the MMP-7 inhibitor and MMP-7 siRNA attenuated CFA-induced lung inflammation and subpleural lung fibrosis. : MMP-7 mediated subpleural lung inflammation as well as fibrosis in RA-ILD. It provided theoretical and experimental support for MMP-7 being a therapeutic target in RA-ILD.
类风湿关节炎相关间质性肺疾病（RA - ILD）是类风湿关节炎的一种严重并发症，缺乏有效的治疗方法，死亡率高。本研究旨在探讨基质金属蛋白酶 - 7（MMP - 7）在介导RA - ILD中的作用。基于RA - ILD患者数据库进行生物信息学分析。模拟了以MMP - 7为中心的蛋白质 - 蛋白质相互作用（PPI）网络。用RA - ILD患者血清或RA - ILD相关炎性因子处理胸膜间皮细胞（PMC），检测Ⅰ型胶原蛋白和MMP - 7的蛋白表达。用完全弗氏佐剂（CFA）建立关节炎模型。记录小鼠体重和关节变化，用Masson染色和天狼星红染色技术评估肺组织。使用MMP - 7抑制剂、MMP - 7 siRNA和MMP shRNA慢病毒抑制MMP - 7，研究体内外Ⅰ型胶原蛋白和纤维化的变化。生物信息学分析发现MMP - 7在RA - ILD肺组织中显著表达，且MMP - 7可能与Ⅰ型胶原蛋白相互作用。体外实验表明细胞因子IL - 1β、IL - 6和TNF - α促进PMC中MMP - 7和Ⅰ型胶原蛋白表达。RA - ILD患者血清也上调PMC中MMP - 7和Ⅰ型胶原蛋白表达。用MMP - 7 siRNA或MMP抑制剂抑制MMP - 7可阻止PMC中Ⅰ型胶原蛋白合成。在体内，CFA诱导大鼠关节炎和胸膜下肺炎症，但MMP - 7抑制剂和MMP - 7 siRNA减轻了CFA诱导的肺炎症和胸膜下肺纤维化。MMP - 7介导RA - ILD中的胸膜下肺炎症和纤维化。这为MMP - 7作为RA - ILD的治疗靶点提供了理论和实验支持。
