PCLAF-DREAM drives alveolar cell plasticity for lung regeneration.
Animals
Regeneration
Mice
Cell Plasticity
/ genetics
Alveolar Epithelial Cells
/ metabolism
Cell Proliferation
Lung
/ pathology
Chloride Channels
/ metabolism
Mice, Inbred C57BL
Transforming Growth Factor beta
/ metabolism
Lung Injury
/ pathology
Pulmonary Fibrosis
/ genetics
Signal Transduction
Humans
Mice, Knockout
Male
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
24 Oct 2024
24 Oct 2024
Historique:
received:
11
10
2022
accepted:
09
10
2024
medline:
25
10
2024
pubmed:
25
10
2024
entrez:
25
10
2024
Statut:
epublish
Résumé
Cell plasticity, changes in cell fate, is crucial for tissue regeneration. In the lung, failure of regeneration leads to diseases, including fibrosis. However, the mechanisms governing alveolar cell plasticity during lung repair remain elusive. We previously showed that PCLAF remodels the DREAM complex, shifting the balance from cell quiescence towards cell proliferation. Here, we find that PCLAF expression is specific to proliferating lung progenitor cells, along with the DREAM target genes transactivated by lung injury. Genetic ablation of Pclaf impairs AT1 cell repopulation from AT2 cells, leading to lung fibrosis. Mechanistically, the PCLAF-DREAM complex transactivates CLIC4, triggering TGF-β signaling activation, which promotes AT1 cell generation from AT2 cells. Furthermore, phenelzine that mimics the PCLAF-DREAM transcriptional signature increases AT2 cell plasticity, preventing lung fibrosis in organoids and mice. Our study reveals the unexpected role of the PCLAF-DREAM axis in promoting alveolar cell plasticity, beyond cell proliferation control, proposing a potential therapeutic avenue for lung fibrosis prevention.
Identifiants
pubmed: 39448571
doi: 10.1038/s41467-024-53330-1
pii: 10.1038/s41467-024-53330-1
doi:
Substances chimiques
Chloride Channels
0
Transforming Growth Factor beta
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
9169Subventions
Organisme : Cancer Prevention and Research Institute of Texas (Cancer Prevention Research Institute of Texas)
ID : RP200315, RP180672, RP200504
Organisme : U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI)
ID : CA193297, CA256207, CA278967, CA278971, CA279867, P50 CA83639, P30 CA016672, CA125123, RR024574
Organisme : U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI)
ID : K99CA286761
Informations de copyright
© 2024. The Author(s).
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