Wang Ziwei, Zhao Hehua
Department of Pediatrics, Beijing Friendship Hospital, Capital Medical University, Beijing, China.
Heliyon. 2024 Jul 30;10(15):e35444. doi: 10.1016/j.heliyon.2024.e35444. eCollection 2024 Aug 15.
Pulmonary fibrosis is a severe and progressive lung disease characterized by the abnormal accumulation of extracellular matrix, leading to scarring and loss of normal lung function. Recent bioinformatics analysis through the Gene Expression Omnibus (GEO) database identified a significant downregulation of Transmembrane Protein 176B (TMEM176B), previously unexplored in the context of fibrotic lung tissues. To investigate the functional role of TMEM176B, we induced pulmonary fibrosis in mice using bleomycin, TGFβ1, and silica, which consistently resulted in a marked decrease in TMEM176B expression. Intriguingly, overexpression of TMEM176B via adenoviral vectors prior to the induction of fibrosis led to significant improvements in fibrotic manifestations and lung function. Mechanistically, TMEM176B appears to mitigate pulmonary fibrosis by inhibiting the TGFβ1-SMAD signaling pathway, which is a critical mediator of fibroblast proliferation and differentiation and promotes extracellular matrix production. These findings suggest that TMEM176B plays an inhibitory role in the pathophysiological processes of pulmonary fibrosis, highlighting its potential as a therapeutic target.
肺纤维化是一种严重的进行性肺部疾病，其特征是细胞外基质异常积聚，导致肺组织瘢痕形成和正常肺功能丧失。最近通过基因表达综合数据库（GEO）进行的生物信息学分析发现，跨膜蛋白176B（TMEM176B）显著下调，而此前在肺纤维化组织中尚未对其进行过研究。为了研究TMEM176B的功能作用，我们使用博来霉素、转化生长因子β1（TGFβ1）和二氧化硅在小鼠中诱导肺纤维化，结果一致显示TMEM176B表达明显降低。有趣的是，在诱导纤维化之前通过腺病毒载体过表达TMEM176B可显著改善纤维化表现和肺功能。从机制上讲，TMEM176B似乎通过抑制TGFβ1 - SMAD信号通路来减轻肺纤维化，该信号通路是成纤维细胞增殖和分化的关键介质，并促进细胞外基质的产生。这些发现表明，TMEM176B在肺纤维化的病理生理过程中起抑制作用，突出了其作为治疗靶点的潜力。
