TRPC6 Channel Regulates Airway Remodeling in Chronic Obstructive Pulmonary Disease Causing Right Heart Failure

Abstract

The role of the canonical transient receptor potential 6 (TRPC6) channel in chronic obstructive pulmonary disease (COPD) remains poorly understood at the mechanistic level.

Objects:

This study aims to investigate the involvement of TRPC6 in COPD and its signaling mechanisms in human airway smooth muscle cells (HASMCs).

Methods and Results:

The study found that mRNA and protein expression of TRPC6 increased in cultured HASMCs that were incubated with nicotine, as measured by reverse transcription quantitative polymerase chain reaction and Western blot analysis. Nicotine treatment significantly enhanced TRPC6 transcriptional activity in HASMCs through nuclear factor (NF)-κB, as demonstrated by co-immunoprecipitation and electrophoretic mobility shift assays. Furthermore, miR-135a/b-5p was shown to downregulate TRPC6 expression in HASMCs at the mRNA and protein levels, as confirmed by luciferase reporter assays. Immunohistochemistry assays in a mouse model of cigarette-induced airway remodeling revealed a significant increase in smooth muscle (SM) cell proliferation and SM layer mass.

Conclusion:

These findings suggest that nicotine exposure increases HASMC proliferation and migration through NF-κB signaling, and that cigarette smoke inhalation causes airway SM layer remodeling via altered TRPC6-induced Ca²⁺ influx, which is abolished by miR-135a/b-5p both in vitro and in vivo. Antioxid. Redox Signal. 42, 480–493.