KCa3.1 differentially regulates trachea and bronchi epithelial gene expression in a chronic-asthma mouse model

Amber R. Philp, Fernando Miranda, Ambra Gianotti, Agustín Mansilla, Paolo Scudieri, Ilaria Musante, Géenesis Vega, Carlos D. Figueroa, Luis J.V. Galietta, Josée M. Sarmiento, Carlos A. Flores*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Ion channels are potentially exploitable as pharmacological targets to treat asthma. This study evaluated the role of KCa3.1 channels, encoded by Kcnn4, in regulating the gene expression of mouse airway epithelium and the development of asthma traits. We used the ovalbumin (OVA) challenge as an asthma model in wild-type and Kcnn4/ mice, performed histological analysis, and measured serum IgE to evaluate asthma traits. We analyzed gene expression of isolated epithelial cells of trachea or bronchi using mRNA sequencing and gene ontology and performed Ussing chamber experiments in mouse trachea to evaluate anion secretion. Gene expression of epithelial cells from mouse airways differed between trachea and bronchi, indicating regional differences in the inflammatory and transepithelial transport properties of proximal and distal airways. We found that Kcnn4 silencing reduced mast cell numbers, mucus, and collagen in the airways, and reduced the amount of epithelial anion secretion in the OVA-challenged animals. In addition, gene expression was differentially modified in the trachea and bronchi, with Kcnn4 genetic silencing significantly altering the expression of genes involved in the TNF pathway, supporting the potential of KCa3.1 as a therapeutic target for asthma.

Original languageEnglish
Pages (from-to)273-282
Number of pages10
JournalPhysiological Genomics
Volume54
Issue number7
DOIs
StatePublished - 2022

Bibliographical note

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© 2022, American Physiological Society. All rights reserved.

ASJC Scopus subject areas

  • Physiology
  • Genetics

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