TGF-alpha/EGFR signalling mediates retinoic acid-induced lung repair
File(s)
Published version
Author(s)
Type
Journal Article
Abstract
Lung repair involves coordination of multicellular processes, including endothelial angiogenesis and epithelial repopulation. Retinoic acid (RA) signalling is crucial for lung development, homeostasis, and repair, however, the mechanisms through which RA drives repair are still unknown. It has previously been shown that RA has no direct effects on repair of alveolar epithelium, yet in animal studies, RA induces alveolar regeneration. Here we show that RA induces endothelial angiogenesis, which is associated with enhanced paracrine signalling to alveolar epithelial cells. Transcriptomic profiling of RA-treated HPMECs undergoing angiogenesis revealed enrichment of wound healing pathways and subsequent in-silico analysis identified several candidate mediators of endothelial-epithelium crosstalk. Scratch assays demonstrated that of these candidates, only TGFα promoted wound healing in alveolar epithelial A549 and primary human alveolar type 2 (hAT2) cells. Mechanistically, TGFα was associated with increased epithelial cell migration and activation of EGFR signalling, without detectable effects on proliferation or apoptosis. Our findings indicate that RA-induced endothelial angiogenesis promotes epithelial EGFR signalling through paracrine mediators, including TGFα. This study highlights the importance of endothelial–epithelial interactions in lung repair and provides insight into pathways that may be targeted to enhance alveolar regeneration.
Date Issued
2026-07-04
Date Acceptance
2026-06-23
Citation
npj Regenerative Medicine, 2026
ISSN
2057-3995
Publisher
Nature Portfolio
Journal / Book Title
npj Regenerative Medicine
Copyright Statement
© The Author(s) 2026. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
License URL
Identifier
10.1038/s41536-026-00492-9
Subjects
Cheong
S.-S.
Yan
C.
Mongey
R. et al. TGF-alpha/EGFR signalling mediates retinoic acidinduced lung repair. npj Regen Med TGF-alpha
retinoic acid
EGFR signalling
angiogenesis
alveolar repair
pulmonary microvascular endothelial cells
lung repair
cell migration
Publication Status
Published online
Date Publish Online
2026-07-04