Language
English
Publication Date
1-1-2024
Journal
Frontiers in Pharmacology
DOI
10.3389/fphar.2024.1433186
PMID
39323641
PMCID
PMC11422212
PubMedCentral® Posted Date
9-11-2024
PubMedCentral® Full Text Version
Post-print
Abstract
Background: Idiopathic pulmonary fibrosis (IPF) is the result of multiple cycles of epithelial cell injury and fibroblast activation; currently, there is no clear etiology. Increasing evidence suggests that protein metabolism and amino acids play a crucial role in IPF, but the role of D-amino acids is not yet clear. The aim of this study was to identify novel mediators in order to test the hypothesis that D-amino acid oxidase (DAO) plays a significant role in the pathogenesis of IPF.
Methods: We analyzed DAO gene expression in patients with IPF and mice with bleomycin (BLM)-induced lung fibrosis. We performed in vitro and in vivo assays to determine the effect of DAO on primary type II alveolar epithelial cells from mice and A549 cells.
Results: DAO expression was downregulated in the lungs of IPF patients and BLM-induced fibrotic mice. Treatment with D-serine (D-Ser) or drug inhibition of DAO promoted cell senescence through the p53/p21 pathway. Dao -/- mice showed an intensified fibrotic response, and the anti-fibrotic role of T3 was abolished.
Conclusion: We concluded that the DAO-p53/p21 axis might be a key anti-fibrotic pathway regulating the progress of fibrosis and facilitating the therapeutic role of T3.
Keywords
idiopathic pulmonary fibrosis, D-amino acid oxidase, triiodothyronine, anti-fibrotic axis, p53/p21 pathway
Published Open-Access
yes
Recommended Citation
Guo, Xiaoshu; Xu, Kai; Wang, Lan; et al., "Triiodothyronine Acts on Dao To Regulate Pulmonary Fibrosis Progression by Facilitating Cell Senescence Through the p53/p21 Signaling Pathway" (2024). Faculty, Staff and Students Publications. 6781.
https://digitalcommons.library.tmc.edu/baylor_docs/6781