Children’s Nutrition Research Center Staff Publications
Language
English
Publication Date
12-17-2023
Journal
Respiratory Research
DOI
10.1186/s12931-023-02633-w
PMID
38105232
PMCID
PMC10726504
PubMedCentral® Posted Date
12-17-2023
PubMedCentral® Full Text Version
Post-print
Abstract
Background: 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.
Methods: 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.
Results: 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 (pY256N-WASP). Furthermore, TUFT1 promoted transforming growth factor-β1 (TGF-β1) induced fibroblast activation by increasing nuclear translocation of pY256N-WASP in fibroblasts, while wiskostatin (Wis), an N-WASP inhibitor, suppressed these processes.
Conclusions: 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.
Keywords
Animals, Mice, Bleomycin, Fibroblasts, Idiopathic Pulmonary Fibrosis, Lung, Lung Diseases, Interstitial, Mice, Inbred C57BL, Stress Fibers, Transforming Growth Factor beta1, IPF, TUFT1, Stress fiber assembly, N-WASP, Cell activation
Published Open-Access
yes
Recommended Citation
Niu, Caoyuan; Xu, Kai; Hu, Yanan; et al., "Tuftelin1 Drives Experimental Pulmonary Fibrosis Progression by Facilitating Stress Fiber Assembly" (2023). Children’s Nutrition Research Center Staff Publications. 315.
https://digitalcommons.library.tmc.edu/staff_pub/315
Included in
Biochemical Phenomena, Metabolism, and Nutrition Commons, Dietetics and Clinical Nutrition Commons, Endocrinology, Diabetes, and Metabolism Commons, Nutrition Commons