An essential function for autocrine hedgehog signaling in epithelial proliferation and differentiation in the trachea.
Animals
Autocrine Communication
/ physiology
Cell Differentiation
Cell Proliferation
Cells, Cultured
Down-Regulation
Embryo, Mammalian
/ cytology
Epithelial Cells
/ cytology
Hedgehog Proteins
/ deficiency
Humans
Lung
/ growth & development
Mice
Mice, Knockout
Signal Transduction
/ genetics
Smoothened Receptor
/ deficiency
Trachea
/ cytology
Transcription Factors
/ genetics
Airway epithelial cells
Smoothened
Sonic hedgehog
Trachea
Tracheomalacia
Journal
Development (Cambridge, England)
ISSN: 1477-9129
Titre abrégé: Development
Pays: England
ID NLM: 8701744
Informations de publication
Date de publication:
01 02 2022
01 02 2022
Historique:
received:
13
05
2021
accepted:
07
12
2021
pubmed:
4
2
2022
medline:
9
3
2022
entrez:
3
2
2022
Statut:
ppublish
Résumé
The tracheal epithelium is a primary target for pulmonary diseases as it provides a conduit for air flow between the environment and the lung lobes. The cellular and molecular mechanisms underlying airway epithelial cell proliferation and differentiation remain poorly understood. Hedgehog (HH) signaling orchestrates communication between epithelial and mesenchymal cells in the lung, where it modulates stromal cell proliferation, differentiation and signaling back to the epithelium. Here, we reveal a previously unreported autocrine function of HH signaling in airway epithelial cells. Epithelial cell depletion of the ligand sonic hedgehog (SHH) or its effector smoothened (SMO) causes defects in both epithelial cell proliferation and differentiation. In cultured primary human airway epithelial cells, HH signaling inhibition also hampers cell proliferation and differentiation. Epithelial HH function is mediated, at least in part, through transcriptional activation, as HH signaling inhibition leads to downregulation of cell type-specific transcription factor genes in both the mouse trachea and human airway epithelial cells. These results provide new insights into the role of HH signaling in epithelial cell proliferation and differentiation during airway development.
Identifiants
pubmed: 35112129
pii: 274222
doi: 10.1242/dev.199804
pmc: PMC8918789
pii:
doi:
Substances chimiques
Hedgehog Proteins
0
Smo protein, mouse
0
Smoothened Receptor
0
Transcription Factors
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
© 2022. Published by The Company of Biologists Ltd.
Déclaration de conflit d'intérêts
Competing interests The authors declare no competing or financial interests.
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