Role of TRPM7 in cardiac fibrosis: A potential therapeutic target (Review)

Cardiac fibrosis is a hallmark of cardiac remodeling associated with nearly all forms of heart disease. Clinically, no effective therapeutic drugs aim to inhibit cardiac fibrosis, owing to the complex etiological heterogeneity and pathogenesis of this disease. A two-in-one protein structure, a ubiquitous expression profile and unique biophysical characteristics enable the involvement of transient receptor potential melastatin-subfamily member 7 (TRPM7) in the pathogenesis and development of fibrosis-related cardiac diseases, such as heart failure (HF), cardiomyopathies, arrhythmia and hyperaldosteronism. In response to a variety of stimuli, multiple bioactive molecules can activate TRPM7 and related signaling pathways, leading to fibroblast proliferation, differentiation and extracellular matrix production in cardiac fibroblasts. TRPM7-mediated Ca(2+) signaling and TGF-β1 signaling pathways are critical for the formation of fibrosis. Accumulating evidence has demonstrated that TRPM7 is a potential pharmacological target for halting the development of fibrotic cardiac diseases. Reliable drug-like molecules for further development of high-affinity in vivo drugs targeting TRPM7 are urgently needed. The present review discusses the widespread and significant role of TRPM7 in cardiac fibrosis and focuses on its potential as a therapeutic target for alleviating heart fibrogenesis.