Skip to content
DraconiticResearch
Search Sources API
197,768 studies31 sourcesUpdated 19 min ago
Peer-reviewedCC BY 4.0NPJ Regenerative Medicine

TGF-alpha/EGFR signalling mediates retinoic acid-induced lung repair

  • Sek-Shir Cheong1
  • Chunyu Yan1
  • Róisín Mongey1
  • David Chambers2
  • Mark Griffiths1,3
  • Matthew Hind1,4
  • Charlotte H. Dean1
4 affiliations
  1. 1National Heart and Lung Institute (NHLI), Imperial College London, London, UK
  2. 2Wolfson Centre for Age Related Diseases, King’s College London, London, UK
  3. 3Peri-Operative Medicine Department, St Bartholomew’s Hospital, London, UK
  4. 4National Institute for Health Research (NIHR) Respiratory Biomedical Research Unit at the Royal Brompton & Harefield NHS Foundation Trust, London, UK
Read full textPDFDOICite

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 the 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.

Related

  1. Dysregulated Platelet GPIb alpha - VWF Signalling in Abdominal Aortic Aneurysm formation and Progression
    T. Feige, A. Bosbach, M. Chario +4
    bioRxivPreprintAll rights reservedFull textGeneral medicinebioRxiv
  2. Dichamanetin attenuates hydrogen peroxide-induced cytotoxicity in retinoic acid (RA) -differentiated human neuroblastoma (SH-SY5Y) cells
    Muhammad-Safuan Zainuddin, Chee-Wei Ang, Saatheeyavaane Bhuvanendran +1
    Beni-Suef University Journal of Basic and Applied SciencesPeer-reviewedCC BYFull textPhysiologyDOAJ
  3. Extracellular vesicle-encapsulated GDF15 alleviates doxorubicin-induced cardiotoxicity via the SUB1/TERT/TPP signalling axis
    Qingqing Gu, Qianwen Chen, Ye Deng +7
    Communications BiologyPeer-reviewedCC BY-NC-ND 4.0Full textCardiovascular medicineCrossref
  4. Skeletal Muscle PGC-1α1 Modulates Kynurenine Metabolism and Mediates Resilience to Stress-Induced Depression
    Leandro Z. Agudelo, Teresa Femenía, Funda Orhan +15
    CellPeer-reviewedLicence not statedFull text739 citedPsychiatry & mental healthHAL
  5. Notch signaling pathway mediates anti-inflammatory effects of vagus nerve stimulation during lipopolysaccharide-induced acute kidney injury
    Shuhei Kuwabara, Hiro Inoue, William T. Nash +7
    Communications BiologyPeer-reviewedCC BY-NC-ND 4.0Full textNeurologyPMC

Cite

BibTeXRIS
BibTeX
@article{cheong2026tgfalphaegfr,
  title = {{TGF-alpha/EGFR signalling mediates retinoic acid-induced lung repair}},
  author = {Sek-Shir Cheong and Chunyu Yan and Róisín Mongey and David Chambers and Mark Griffiths and Matthew Hind and Charlotte H. Dean},
  journal = {NPJ Regenerative Medicine},
  year = {2026},
  month = jul,
  doi = {10.1038/s41536-026-00492-9},
  url = {https://doi.org/10.1038/s41536-026-00492-9},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - TGF-alpha/EGFR signalling mediates retinoic acid-induced lung repair
AU  - Sek-Shir Cheong
AU  - Chunyu Yan
AU  - Róisín Mongey
AU  - David Chambers
AU  - Mark Griffiths
AU  - Matthew Hind
AU  - Charlotte H. Dean
PY  - 2026
DA  - 2026/07/04
JO  - NPJ Regenerative Medicine
DO  - 10.1038/s41536-026-00492-9
UR  - https://doi.org/10.1038/s41536-026-00492-9
AB  - 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 the 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.
SN  - 2057-3995
ER  -