Wnt5a/ß-catenin axis is involved in the downregulation of AT2 lineage by PAI-1.
Am J Physiol Lung Cell Mol Physiol
; 323(5): L515-L524, 2022 Nov 01.
Article
in English
| MEDLINE | ID: covidwho-2108362
ABSTRACT
Failure to regenerate injured alveoli functionally and promptly causes a high incidence of fatality in coronavirus disease 2019 (COVID-19). How elevated plasminogen activator inhibitor-1 (PAI-1) regulates the lineage of alveolar type 2 (AT2) cells for re-alveolarization has not been studied. This study aimed to examine the role of PAI-1-Wnt5a-ß catenin cascades in AT2 fate. Dramatic reduction in AT2 yield was observed in Serpine1Tg mice. Elevated PAI-1 level suppressed organoid number, development efficiency, and total surface area in vitro. Anti-PAI-1 neutralizing antibody restored organoid number, proliferation and differentiation of AT2 cells, and ß-catenin level in organoids. Both Wnt family member 5A (Wnt5a) and Wnt5a-derived N-butyloxycarbonyl hexapeptide (Box5) altered the lineage of AT2 cells. This study demonstrates that elevated PAI-1 regulates AT2 proliferation and differentiation via the Wnt5a/ß catenin cascades. PAI-1 could serve as autocrine signaling for lung injury repair.
Keywords
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Plasminogen Activator Inhibitor 1
/
Beta Catenin
/
Wnt-5a Protein
/
COVID-19
Type of study:
Observational study
Limits:
Animals
Language:
English
Journal:
Am J Physiol Lung Cell Mol Physiol
Journal subject:
Molecular Biology
/
Physiology
Year:
2022
Document Type:
Article
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