Transient receptor potential melastatin 7 (TRPM7) contributes to H 2O2-induced cardiac fibrosis via mediating Ca2+ influx and extracellular signal-regulated kinase 1/2 (ERK1/2) activation in cardiac fibroblasts

Transient receptor potential melastatin 7 (trpm7),a ca2+- nonselective cation channel,plays a key role in the pathophysiological response of multiple cell types. however,the role of trpm7 channels in hydrogen peroxide (h2o2)-induced cardiac fibrosis remains unclear. this study aimed to explore whether trpm7 channels are involved in h 2o2-induced cardiac fibrosis and the underlying mechanisms. our results showed that 2-aminoethoxydiphenylborate (2-apb),which is commonly used to block trpm7 channels,inhibited h2o 2-induced cardiac fibrosis via attenuating the overexpression of important fibrogenic biomarkers and growth factors in cardiac fibroblasts,including collagen type i (col i),fibronectin (fn),smooth muscle α-actin (α-sma),connective tissue growth factor (ctgf),and transforming growth factor-β1 (tgf-β1). in addition,2-apb also decreased h 2o2-mediated elevation of the concentration of intracellular ca2+ ([ca2+]i). meanwhile,silencing trpm7 channels by shrna interference also impaired the increased [ca2+]i and upregulation of col?i,fn,α-sma,ctgf,and tgf- β1 induced by h2o2. furthermore,we found that h2o 2-mediated activation of extracellular signal-regulated kinase 1/2 (erk1/2) decreased in trpm7-shrna cells and ca2+-free culture media. these results demonstrated that trpm7 channels contributed to h 2o2-induced cardiac fibrosis and suggested that this contribution may be through mediating ca2+ influx and phosphorylation of erk1/2. © the japanese pharmacological society.