Tiotropium inhibits methacholine-induced extracellular matrix production via β-catenin signaling in human airway smooth muscle cells

International Journal of Chronic Obstructive Pulmonary Disease
Yating HuoRongchang Chen

Abstract

Airway remodeling is an important feature of chronic obstructive pulmonary disease (COPD) that is associated with disease severity and irreversible airflow limitation. An extensive alteration of the extracellular matrix (ECM) surrounding the airway smooth muscle (ASM) bundle is one of the pathological manifestations of airway remodeling, which contributes to the decline in lung function. Tiotropium, a long-acting inhaled muscarinic receptor antagonist, has been confirmed to play a role in preventing airway remodeling including ECM deposition beyond bronchodilation in vivo, but the relationship between ASM cell (ASMC) relaxation and ECM production remains unclear. In this study, we attempted to investigate the influence of tiotropium on ECM production by ASMCs and the underlying mechanism. Tiotropium was added 30 minutes before the addition of methacholine to primary cultured human ASMCs. Protein expression was analylized by Western Blot and mRNA abundance was determined by real-time PCR. We found that tiotropium reduced collagen I protein expression, and the mRNA abundance of collagen I, fibronectin, and versican. β-catenin signaling was inactivated by inhibiting glycogen synthase kinase 3β (GSK3β) phosphorylation in this proce...Continue Reading

Citations

Oct 23, 2019·Signal Transduction and Targeted Therapy·Seyyed Shamsadin Athari
Feb 10, 2021·Allergy·Mario CazzolaMaria Gabriella Matera
Oct 18, 2020·Signal Transduction and Targeted Therapy·Seyyed Shamsadin Athari
Aug 25, 2021·Yonsei Medical Journal·Xiangying WangMeiling Sheng

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Methods Mentioned

BETA
PCR
Protein Assay
electrophoresis
transfection

Software Mentioned

ImageJ
SPSS

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