Canonical transient receptor potential 3 channels activate NF-κB to mediate allergic airway disease via PKC-α/IκB-α and calcineurin/IκB-β pathways

Tengyao Song, Yun Min Zheng, Peter A. Vincent, Dongsheng Cai, Paul Rosenberg, Yong Xiao Wang

Research output: Contribution to journalArticle

11 Scopus citations

Abstract

The purpose of this study was to determine the role of canonical transient receptor potential 3 (TRPC3) channel in allergen-induced airway disease (AIAD) and its underlying signaling mechanisms. The procedures included (1) intravenous injection of lentiviral TRPC3 channel or nonsilencing short hairpin ribonucleic acid (shRNA) to make the channel knockdown (KD) or control mice, (2) allergen sensitization/challenge to induce AIAD, (3) patch-clamp recording and Ca2+ imaging to examine the channel activity, and (4) gene manipulations and other methods to determine the underlying signaling mechanisms. The findings are that (1) intravenous or intranasal delivery of TRPC3 channel lentiviral shRNAs or blocker 1-[4-[(2,3,3-trichloro-1-oxo-2-propen-1-yl)amino] phenyl]-5-(trifluoromethyl)-1H-pyrazole-4-carboxylic acid prevents AIAD in mice, (2) TRPC3 channel KD and overexpression, respectively, blocks and augments protein kinase C-α/nuclear factor of κ light polypeptide gene enhancer in B-cell inhibitor-α (PKC-α/IκB-α)-mediated or calcineurin/IκB-β-dependent, NF-κB-dependent allergen-induced airway smooth muscle cell (ASMC) hyperproliferation and cyclin D1 (an important cell proliferation molecule) induction, and (3) the changes of the major molecules of the PKC-α/IκBα- and calcineurin/IκB-β-dependent NF-κB signaling pathways are also observed in asthmatic human ASMCs. The conclusions are that TRPC3 channels plays an essential role in AIAD via the PKC-α/IκB-α- and calcineurin/IκB-β-dependent NF-κB signaling pathways, and lentiviral shRNA or inhibitor of TRPC3 channels may become novel and effective treatments for AIAD.

Original languageEnglish (US)
Pages (from-to)214-229
Number of pages16
JournalFASEB Journal
Volume30
Issue number1
DOIs
StatePublished - Jan 1 2016

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Keywords

  • AIAD
  • Ion channel
  • Signaling pathway

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics

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