Wnt5a/β-catenin axis is involved in the downregulation of AT2 lineage by PAI-1

Autor:	Krishan G. Jain, Runzhen Zhao, Yang Liu, Xuan Guo, Guohua Yi, Hong-Long Ji
Rok vydání:	2022
Předmět:	Pulmonary and Respiratory Medicine Physiology COVID-19 Down-Regulation Cell Biology Antibodies Neutralizing Wnt-5a Protein Pulmonary Alveoli Mice Physiology (medical) Plasminogen Activator Inhibitor 1 Animals Wnt Signaling Pathway beta Catenin Cell Proliferation
Zdroj:	American Journal of Physiology-Lung Cellular and Molecular Physiology. 323:L515-L524
ISSN:	1522-1504 1040-0605
DOI:	10.1152/ajplung.00202.2022
Popis:	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-β 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 β-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/β catenin cascades. PAI-1 could serve as autocrine signaling for lung injury repair.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::6e7d88fd13d88c42f7f81d5d0549939c https://doi.org/10.1152/ajplung.00202.2022 Zobrazit plný text záznamu