title: TRPM7 channels mediate the functional changes in cardiac fibroblasts induced by angiotensin II.
abstract: Transient receptor potential melastatin 7 (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 angiotensin II (Ang II) 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 Ang II. Our data showed that Ang II 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 Ang II. Our results identified the TRPM7 channel as a pivotal member associated with the functional change of CFs induced by Ang II, and suggest that the TRPM7 channel may represent a promising therapeutic strategy for the treatment of fibrosis-related cardiac diseases.
authors.affiliation: Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China.
authors.forename: Sha
authors.initials: S
authors.lastname: Li
authors.affiliation: Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China.
authors.forename: Mingjiang
authors.initials: M
authors.lastname: Li
authors.affiliation: Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China.
authors.forename: Xin
authors.initials: X
authors.lastname: Yi
authors.affiliation: Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China.
authors.forename: Furong
authors.initials: F
authors.lastname: Guo
authors.affiliation: Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China.
authors.forename: Yanli
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China.
authors.forename: Suqin
authors.initials: S
authors.lastname: Chen
authors.affiliation: Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China.
authors.forename: Xian
authors.initials: X
authors.lastname: Wu
mesh_terms: D000804:Angiotensin II / Q000378:metabolism* / Q000494:pharmacology; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D003094:Collagen / Q000096:biosynthesis; D015870:Gene Expression; D020868:Gene Silencing; D015640:Ion Channel Gating / Q000235:genetics; D058628:Myofibroblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics; D051381:Rats; D050053:TRPM Cation Channels / Q000235:genetics / Q000378:metabolism*
chemical_list: D034741:RNA, Small Interfering; D050053:TRPM Cation Channels; D000804:Angiotensin II; D003094:Collagen; C486584:Trpm7 protein, rat