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