Wnt5a/β-catenin axis is involved in the downregulation of AT2 lineage by PAI-1.
| Autor: | Jain KG; Department of Cellular and Molecular Biology, University of Texas at Tyler, Tyler, Texas., Zhao R; Department of Cellular and Molecular Biology, University of Texas at Tyler, Tyler, Texas., Liu Y; Department of Cellular and Molecular Biology, University of Texas at Tyler, Tyler, Texas., Guo X; Department of Computer Science and Engineering, University of North Texas, Denton, Texas., Yi G; Department of Pulmonary Immunology, University of Texas at Tyler, Tyler, Texas., Ji HL; Department of Cellular and Molecular Biology, University of Texas at Tyler, Tyler, Texas.; Texas Lung Injury Institute, University of Texas at Tyler, Tyler, Texas. |
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| Jazyk: | angličtina |
| Zdroj: | American journal of physiology. Lung cellular and molecular physiology [Am J Physiol Lung Cell Mol Physiol] 2022 Nov 01; Vol. 323 (5), pp. L515-L524. Date of Electronic Publication: 2022 Sep 13. |
| DOI: | 10.1152/ajplung.00202.2022 |
| Abstrakt: | 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 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 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: | MEDLINE |
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