TMEM176B Prevents and alleviates bleomycin-induced pulmonary fibrosis via inhibiting transforming growth factor β-Smad signaling

Autor: Ziwei Wang, Hehua Zhao
Jazyk: angličtina
Rok vydání: 2024
Předmět:
Zdroj: Heliyon, Vol 10, Iss 15, Pp e35444- (2024)
Druh dokumentu: article
ISSN: 2405-8440
DOI: 10.1016/j.heliyon.2024.e35444
Popis: 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.
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