The role of TRP channels in lung fibrosis: Mechanisms and therapeutic potential

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 • Idiopathic Pulmonary Fibrosis (IPF): A progressive and fatal lung disease marked by fibroblast-to-myofibroblast transition, leading to excessive extracellular matrix (ECM) deposition and tissue scarring. • TRP Channels in Fibrosis: TRP (Transient Receptor Potential) channels, specifically TRPA1, TRPV4, TRPC6, and TRPM7, are emerging as key regulators in fibrosis, modulating Ca²⁺ signalling, myofibroblast activation, and ECM production. • Fibrotic Mechanisms: TRP channels influence essential processes like mechanical stress sensing and pro-fibrotic signalling pathways (e.g., TGFβ), making them potential therapeutic targets for halting or reversing fibrosis progression. • Therapeutic Potential: Targeting TRP channels may offer novel strategies to disrupt fibroblast-to-myofibroblast transition, thus preventing or mitigating IPF and other fibrotic diseases.