TRPM7 channels mediate the functional changes in cardiac fibroblasts induced by angiotensin II.

Abstract

Transient receptor potential melastatin7 (TRPM7), a bifunctional channel protein owning both cation permeability and kinase activity, plays an important role in the pathophysiological process of many cell types, such as vascular smooth muscle cells, human glioma cells and mouse cortical astrocytes. However, whether TRPM7 channels play a key role in the functional change of cardiac fibroblasts(CFs) induced by angiotensinII (AngII) remains unknown. Using Cell Counting Kit-8 (CCK-8) assay, immunofluorescence assay, western blot analysis, RT-qPCR, RNA interference(RNAi) and whole-cell patch-clamp techniques, the present study aimed to explore the role of TRPM7 channels in the proliferation, differentiation and collagen synthesis of CFs induced by AngII. Our data showed that AngII time-dependently increased TRPM7 expression and TRPM7 currents in the CFs. Downregulation of TRPM7 attenuated the TRPM7 current density, and inhibited the proliferation, differentiation and collagen synthesis of CFs induced by AngII. Our results identified the TRPM7 channel as a pivotal member associated with the functional change of CFs induced by AngII, and suggest that the TRPM7 channel may represent a promising therapeutic strategy for the treatment of fibrosis-related cardiac diseases.