| First Author | Jain KG | Year | 2022 |
| Journal | Am J Physiol Lung Cell Mol Physiol | Volume | 323 |
| Issue | 5 | Pages | L515-L524 |
| PubMed ID | 36098461 | Mgi Jnum | J:329972 |
| Mgi Id | MGI:7356198 | Doi | 10.1152/ajplung.00202.2022 |
| Citation | Jain KG, et al. (2022) Wnt5a/beta-catenin axis is involved in the downregulation of AT2 lineage by PAI-1. Am J Physiol Lung Cell Mol Physiol 323(5):L515-L524 |
| abstractText | 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-beta catenin cascades in AT2 fate. Dramatic reduction in AT2 yield was observed in Serpine1(Tg) 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 beta-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/beta catenin cascades. PAI-1 could serve as autocrine signaling for lung injury repair. |
