Research Paper Advance Articles

Core fucosylation regulates alveolar epithelial cells senescence through activating of transforming growth factor-β pathway in pulmonary fibrosis

Yu Jiang1, *, , Zhongzhen Wang2, *, , Jinying Hu1, , Wei Wang3, , Na Zhang1, , Lili Gao1, ,

  • 1 Department of Respiratory Medicine, The First Affiliated Hospital of Dalian Medical University, Dalian, China
  • 2 Department of Cardiology, Institute of Cardiovascular Diseases, The First Affiliated Hospital of Dalian Medical University, Dalian, China
  • 3 Department of Nephrology, Affiliated Xinhua Hospital of Dalian University, Dalian, China
* Equal contribution and co-first authors

Received: February 2, 2023       Accepted: August 24, 2023       Published: September 18, 2023      

https://doi.org/10.18632/aging.205036
How to Cite

Copyright: © 2023 Jiang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Idiopathic pulmonary fibrosis (IPF), a fatal disorder associated with aging, has a terrible prognosis. However, the potential causes of IPF remain a riddle. In this study, we designed to explore whether the modification of the core fucosylation (CF) can ameliorate pulmonary fibrosis by targeting alveolar epithelial cells (AECs) senescence. First, we verified that cellular senescence occurs in the bleomycin-induced lung fibrosis mice models and CF modifications accompanying senescent AECs in pulmonary fibrosis. Next, both gain- and loss- of function research on CF were performed to elucidate its role in promoting AECs senescence and triggering pulmonary fibrosis in vitro. Notably, using alveolar epithelial cell-specific FUT8 conditional knockout mouse models, however, inhibition of cellular senescence by deleting the FUT8 gene could attenuate pulmonary fibrosis in vivo. Finally, blocking the CF modification of transforming growth factor -β type I receptor (TGF-βR I) could reduce the activation of downstream transforming growth factor -β (TGF-β) pathways in AECs senescence both in vivo and in vitro. This study reveals that CF is a crucial interventional target for the treatment of pulmonary fibrosis. Blocking CF modification contributes importantly to inhibiting AECs senescence resulting in pulmonary fibrosis lessen.

Abbreviations

IPF: idiopathic pulmonary fibrosis; CF: core fucosylation; AECs: alveolar epithelial cells; MLE12: murine lung epithelial-12; FUT8: α1,6-fucosyltransferase; TGF-β: transforming growth factor-β; TGF-βR I: transforming growth factor-β type I receptor; CKO: alveolar epithelial cell-specific FUT8 conditional knockout; BLM: bleomycin; SA-β-gal: senescence associated-β-galactosidase; SPC: surfactant protein C; LCA: lens culinaris agglutinin; SASP: senescence-associated secretory phenotype.