TRPC1 intensifies house dust mite-induced airway remodeling by facilitating epithelial-to-mesenchymal transition and STAT3/NF-κB signaling.
FASEB J
; 33(1): 1074-1085, 2019 01.
Article
em En
| MEDLINE
| ID: mdl-30067380
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 with decreases in mucus production, cytokine secretion, and collagen deposition. HDM challenge induces 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 TRPC1-/- mouse lungs compared with wild-type controls after HDM challenge. Mechanistically, STAT3 promotes epithelial-to-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.-Pu, Q., Zhao, Y., Sun, Y., Huang, T., Lin, P., Zhou, C., Qin, S., Singh, B. B., Wu, M. TRPC1 intensifies house dust mite-induced airway remodeling by facilitating epithelial-to-mesenchymal transition and STAT3/NF-κB signaling.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Transdução de Sinais
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NF-kappa B
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Pyroglyphidae
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Fator de Transcrição STAT3
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Canais de Cátion TRPC
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Remodelação das Vias Aéreas
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Transição Epitelial-Mesenquimal
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article