The Role of TRP Channels in Lung Fibrosis: Mechanisms and Therapeutic Potential

M Ratnasingham; P Bradding; K M Roach

doi:10.1016/j.biocel.2024.106728

The Role of TRP Channels in Lung Fibrosis: Mechanisms and Therapeutic Potential

Int J Biochem Cell Biol. 2024 Dec 11:106728. doi: 10.1016/j.biocel.2024.106728. Online ahead of print.

Authors

M Ratnasingham¹, P Bradding¹, K M Roach²

Affiliations

¹ NIHR Respiratory BRC, Department of Respiratory Sciences, University of Leicester, Leicester, UK.
² NIHR Respiratory BRC, Department of Respiratory Sciences, University of Leicester, Leicester, UK. Electronic address: kmr11@leicester.ac.uk.

PMID: 39672503
DOI: 10.1016/j.biocel.2024.106728

Abstract

Idiopathic pulmonary fibrosis (IPF) is a severe lung disease affecting around 5 million people globally, with a median survival of 3-4 years. Characterized by excessive scarring of lung tissue, IPF results from the accumulation of myofibroblasts that deposit extracellular matrix (ECM), causing fibrosis. Current treatments, pirfenidone and nintedanib, slow the disease but do not stop its progression. IPF pathogenesis involves repeated alveolar injury, leading to pro-fibrotic mediators like TGFβ1, which trigger fibroblast-to-myofibroblast transitions and ECM deposition. Recent research suggests that transient receptor potential (TRP) channels, such as TRPV4, TRPC6, and TRPA1, play a key role in regulating calcium signalling and mechanical stress, crucial in myofibroblast activation. Targeting TRP channels may disrupt fibrosis and offer new therapeutic strategies. Preclinical studies indicate that inhibiting TRP channels could reduce fibrosis, warranting further trials to explore their efficacy and safety in treating IPF and related fibrotic conditions.

Keywords: Fibrosis; Idiopathic Pulmonary Fibrosis; Ion channels; Therapeutic targets; Transient receptor potential (TRP) channels.