Dynamic Expression of Transient Receptor Potential Vanilloid-3 and Integrated Signaling with Growth Factor Pathways during Lung Epithelial Wound Repair following Wood Smoke Particle and Other Forms of Lung Cell Injury.

Autor:	Burrell KL; Department of Pharmacology and Toxicology, Center for Human Toxicology, University of Utah, Salt Lake City, Utah., Nguyen ND; Department of Pharmacology and Toxicology, Center for Human Toxicology, University of Utah, Salt Lake City, Utah., Deering-Rice CE; Department of Pharmacology and Toxicology, Center for Human Toxicology, University of Utah, Salt Lake City, Utah., Memon TA; Department of Pharmacology and Toxicology, Center for Human Toxicology, University of Utah, Salt Lake City, Utah., Almestica-Roberts M; Department of Pharmacology and Toxicology, Center for Human Toxicology, University of Utah, Salt Lake City, Utah., Rapp E; Department of Pharmacology and Toxicology, Center for Human Toxicology, University of Utah, Salt Lake City, Utah., Serna SN; Department of Pharmacology and Toxicology, Center for Human Toxicology, University of Utah, Salt Lake City, Utah., Lamb JG; Department of Pharmacology and Toxicology, Center for Human Toxicology, University of Utah, Salt Lake City, Utah., Reilly CA; Department of Pharmacology and Toxicology, Center for Human Toxicology, University of Utah, Salt Lake City, Utah Chris.Reilly@pharm.utah.edu.
Jazyk:	angličtina
Zdroj:	Molecular pharmacology [Mol Pharmacol] 2021 Sep; Vol. 100 (3), pp. 295-307. Date of Electronic Publication: 2021 Jul 21.
DOI:	10.1124/molpharm.121.000280
Abstrakt:	Prior studies revealed increased expression of the transient receptor potential vanilloid-3 (TRPV3) ion channel after wood smoke particulate matter (WSPM) treatment of human bronchial epithelial cells (HBECs). TRPV3 attenuated pathologic endoplasmic reticulum stress and cytotoxicity mediated by transient receptor potential ankyrin-1. Here, the basis for how TRPV3 expression is regulated by cell injury and the effects this has on HBEC physiology and WSPM-induced airway remodeling in mice was investigated. TRPV3 mRNA was rapidly increased in HBECs treated with WSPM and after monolayer damage caused by tryptic disruption, scratch wounding, and cell passaging. TRPV3 mRNA abundance varied with time, and stimulated expression occurred independent of new protein synthesis. Overexpression of TRPV3 in HBECs reduced cell migration and wound repair while enhancing cell adhesion. This phenotype correlated with disrupted mRNA expression of ligands of the epidermal growth factor, tumor growth factor- β , and frizzled receptors. Accordingly, delayed wound repair by TRPV3 overexpressing cells was reversed by growth factor supplementation. In normal HBECs, TRPV3 upregulation was triggered by exogenous growth factor supplementation and was attenuated by inhibitors of growth factor receptor signaling. In mice, subacute oropharyngeal instillation with WSPM also promoted TRPV3 mRNA expression and epithelial remodeling, which was attenuated by TRPV3 antagonist pre- and cotreatment. This latter effect may be the consequence of antagonist-induced TRPV3 expression. These findings provide insights into the roles of TRPV3 in lung epithelial cells under basal and dynamic states, as well as highlight potential roles for TRPV3 ligands in modulating epithelial damage/repair. SIGNIFICANCE STATEMENT: Coordinated epithelial repair is essential for the maintenance of the airways, with deficiencies and exaggerated repair associated with adverse consequences to respiratory health. This study shows that TRPV3, an ion channel, is involved in coordinating repair through integrated repair signaling pathways, wherein TRPV3 expression is upregulated immediately after injury and returns to basal levels as cells complete the repair process. TRPV3 may be a novel target for understanding and/or treating conditions in which airway/lung epithelial repair is not properly orchestrated. (Copyright © 2021 by The American Society for Pharmacology and Experimental Therapeutics.)
Databáze:	MEDLINE
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