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

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

American journal of physiology. Lung cellular and molecular physiology (2022-09-14)

Krishan G Jain, Runzhen Zhao, Yang Liu, Xuan Guo, Guohua Yi, Hong-Long Ji

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-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.

MATERIALS

Product Number

Brand

Product Description

681673

Sigma-Aldrich

Wnt Antagonist III, Box5, The Wnt Antagonist III, Box5 controls the biological activity of Wnt. This small molecule/inhibitor is primarily used for Cancer applications.