Single-Cell RNA Sequencing Provides New Insights into Therapeutic Roles of Thyroid Hormone in Idiopathic Pulmonary Fibrosis

Authors

• Lan Wang
• Zhongzheng Li
• Ruyan Wan
• Xin Pan
• Bin Li
• Huabin Zhao
• Juntang Yang
• Weiming Zhao
• Shenghui Wang
• Qiwen Wang
• Peishuo Yan
• Chi Ma
• Hongmei Yuan
• Mengxia Zhao
• Ivan Rosas
• Chen Ding
• Baofa Sun
• Guoying Yu

Language

English

Publication Date

10-1-2023

Journal

American Journal of Respiratory Cell and Molecular Biology

DOI

10.1165/rcmb.2023-0080OC

PMID

37402274

PMCID

PMC10557923

PubMedCentral® Posted Date

7-4-2023

PubMedCentral® Full Text Version

Post-print

Abstract

Idiopathic pulmonary fibrosis (IPF) is a progressive fatal interstitial lung disease without an effective cure. Herein, we explore the role of 3,5,3′-triiodothyronine (T3) administration on lung alveolar regeneration and fibrosis at the single-cell level. T3 supplementation significantly altered the gene expression in fibrotic lung tissues. Immune cells were rapidly recruited into the lung after the injury; there were much more M2 macrophages than M1 macrophages in the lungs of bleomycin-treated mice; and M1 macrophages increased slightly, whereas M2 macrophages were significantly reduced after T3 treatment. T3 enhanced the resolution of pulmonary fibrosis by promoting the differentiation of Krt8+ transitional alveolar type II epithelial cells into alveolar type I epithelial cells and inhibiting fibroblast activation and extracellular matrix production potentially by regulation of Nr2f2. In addition, T3 regulated the crosstalk of macrophages with fibroblasts, and the Pros1-Axl signaling axis significantly facilitated the attenuation of fibrosis. The findings demonstrate that administration of a thyroid hormone promotes alveolar regeneration and resolves fibrosis mainly by regulation of the cellular state and cell-cell communication of alveolar epithelial cells, macrophages, and fibroblasts in mouse lungs in comprehensive ways.

Keywords

Mice, Animals, Idiopathic Pulmonary Fibrosis, Lung, Fibrosis, Bleomycin, Fibroblasts, Thyroid Hormones, Sequence Analysis, RNA, pulmonary fibrosis, T3 therapy, single-cell RNA-seq, cell-cell communication, gene regulatory network

Published Open-Access

yes

Recommended Citation

Wang, Lan; Li, Zhongzheng; Wan, Ruyan; et al., "Single-Cell RNA Sequencing Provides New Insights into Therapeutic Roles of Thyroid Hormone in Idiopathic Pulmonary Fibrosis" (2023). Faculty, Staff and Students Publications. 6782.
https://digitalcommons.library.tmc.edu/baylor_docs/6782