Figure 3.

Schematic diagram of TRPM7 structure and cardiac fibroblast signalling. (A) Basic structure of alpha subunit of TRPM7. Each TRPM7 alpha subunit is comprised of six transmembrane-spanning domains (S1–S6), with a pore loop between S5 and S6, melastatin homology domains (MHD) at the amino termini, and a TRP-box (TRP), a coiled-coil domain (CCD), and an atypical α-type serine/threonine protein kinase domain (α-kinase) at the carboxyl termini. (B) Known TRPM7 homotetrameric ion channel signalling in cardiac fibroblasts. Ang II drives activation of TRPM7 and is coupled to increased nuclear activity of Ki-67 and proliferating cell nuclear antigen (PCNA), as well as upregulation of markers of fibrosis including connective tissue growth factor (CTGF). H₂O₂ activates TRPM7 and promotes MF differentiation and ECM remodelling via the ERK-1/2 MAP kinase pathway. TGF-β1 and isoproterenol treatment both induce upregulation of TRPM7 expression and Ca²⁺ influx leading to myofibroblast differentiation. TRPM7 expression can be inhibited by miR-135a expression. See main text for details.