Tuftelin1 drives experimental pulmonary fibrosis progression by facilitating stress fiber assembly

• Published in: Respiratory research Vol. 24; no. 1; p. 318
• Main Authors: Niu, Caoyuan, Xu, Kai, Hu, Yanan, Jia, Yanling, Yang, Yuexia, Pan, Xiaoyue, Wan, Ruyan, Lian, Hui, Wang, Qiwen, Yang, Juntang, Li, Yajun, Rosas, Ivan, Wang, Lan, Yu, Guoying
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 17.12.2023; BioMed Central; BMC
• Subjects: Analysis; Animal models; Animals; Antibiotics; Assembly; Biological markers; Bleomycin; Bleomycin - toxicity; Cancer; Cell activation; Cytoskeleton; Development and progression; Disease; Epithelial cells; Epithelium; Fibroblasts; Fibroblasts - metabolism; Fibrosis; Gene expression; Genetic aspects; Growth factors; Idiopathic Pulmonary Fibrosis - chemically induced; Idiopathic Pulmonary Fibrosis - metabolism; IPF; Laboratory animals; Lung - metabolism; Lung diseases; Lung Diseases, Interstitial - metabolism; Medical imaging; Mice; Mice, Inbred C57BL; Microfilaments; Molecular mechanics; Molecular modelling; N-WASP; Nuclear transport; Penicillin; Phenotypes; Phosphorylation; Prognosis; Pulmonary fibrosis; Stress fiber assembly; Stress Fibers - metabolism; Transforming Growth Factor beta1 - pharmacology; Transforming growth factor-b1; Translocation; TUFT1; Tyrosine; Wiskott-Aldrich syndrome; Wound healing; China; Belgium; United States > US; Cell activation; N-WASP; Stress fiber assembly; TUFT1; IPF
• ISSN: 1465-993X; 1465-9921; 1465-993X; 1465-9921
• DOI: 10.1186/s12931-023-02633-w

Idiopathic pulmonary fibrosis (IPF) is a progressive interstitial lung disease (ILD) with unknown etiology, characterized by sustained damage repair of epithelial cells and abnormal activation of fibroblasts, the underlying mechanism of the disease remains elusive. To evaluate the role of Tuftelin1 (TUFT1) in IPF and elucidate its molecular mechanism. We investigated the level of TUFT1 in the IPF and bleomycin-induced mouse models and explored the influence of TUFT1 deficiency on pulmonary fibrosis. Additionally, we explored the effect of TUFT1 on the cytoskeleton and illustrated the relationship between stress fiber and pulmonary fibrosis. Our results demonstrated a significant upregulation of TUFT1 in IPF and the bleomycin (BLM)-induced fibrosis model. Disruption of TUFT1 exerted inhibitory effects on pulmonary fibrosis in both in vivo and in vitro. TUFT1 facilitated the assembly of microfilaments in A549 and MRC-5 cells, with a pronounced association between TUFT1 and Neuronal Wiskott-Aldrich syndrome protein (N-WASP) observed during microfilament formation. TUFT1 can promote the phosphorylation of tyrosine residue 256 (Y256) of the N-WASP (p N-WASP). Furthermore, TUFT1 promoted transforming growth factor-β1 (TGF-β1) induced fibroblast activation by increasing nuclear translocation of p N-WASP in fibroblasts, while wiskostatin (Wis), an N-WASP inhibitor, suppressed these processes. Our findings suggested that TUFT1 plays a critical role in pulmonary fibrosis via its influence on stress fiber, and blockade of TUFT1 effectively reduces pro-fibrotic phenotypes. Pharmacological targeting of the TUFT1-N-WASP axis may represent a promising therapeutic approach for pulmonary fibrosis.