TRPC1 intensifies house dust mite-induced airway remodeling by facilitating epithelial-to-mesenchymal transition and STAT3/NF-κB signaling

Qinqin Pu, Yuanyu Zhao, Yuyang Sun, Ting Huang, Ping Lin, Chuanmin Zhou, Shugang Qin, Brij B. Singh, Min Wu

Research output: Contribution to journalArticle

4 Scopus citations

Abstract

Airway remodeling with progressive epithelial alterations in the respiratory tract is a severe consequence of asthma. Although dysfunctional signaling transduction is attributed to airway inflammation, the exact mechanism of airway remodeling remains largely unknown. TRPC1, a member of the transient receptor potential canonical Ca2+ channel family, possesses versatile functions but its role in airway remodeling remains undefined. Here, we show that ablation of TRPC1 in mice alleviates airway remodeling following house dust mite (HDM) challenge withdecreases inmucus production, cytokine secretion, and collagen deposition. HDM challengeinduces Ca2+ influx via the TRPC1 channel, resulting in increased levels of signal transducer and activator of transcription 3 (STAT3) and proinflammatory cytokines. In contrast, STAT3 expression was significantly decreased in TRPC12/2 mouse lungs compared with wild-type controls after HDM challenge. Mechanistically, STAT3 promotes epithelialto-mesenchymal transition and increases mucin 5AC expression. Collectively, these findings identify TRPC1 as a modulator of HDM-induced airway remodeling via STAT3-mediated increase in mucus production, which provide new insight in our understanding of the molecular basis of airway remodeling, and identify novel therapeutic targets for intervention of severe chronic asthma.

Original languageEnglish (US)
Pages (from-to)1074-1085
Number of pages12
JournalFASEB Journal
Volume33
Issue number1
DOIs
StatePublished - Jan 2019

Keywords

  • Asthma
  • Cell signaling
  • Ion channel
  • Transcription factors

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics

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