title: TRPM7 is involved in angiotensin II induced cardiac fibrosis development by mediating calcium and magnesium influx.
abstract: Cardiac fibrosis is involved in a lot of cardiovascular pathological processes. Cardiac fibrosis can block conduction, cause hypoxia, strengthen myocardial stiffness, create electrical heterogeneity, and hamper systolic ejection, which is associated with the development of arrhythmia, heart failure and sudden cardiac death. Besides the initial stimulating factors, the cardiac fibroblasts (CFs) are the principal responsible cells in the fibrogenesis cascade of events. TRPM7, a member of the TRPM (Melastatin) subfamily, is a non-selective cation channel, which permeates both Ca(2+) and Mg(2+). Here we demonstrated TRPM7 expression in CFs, and 2-APB (TRPM7 inhibitor), inhibited Ang II-induced CTGF, α-SMA expression and CFs proliferation. Besides, knocking down TRPM7 by shRNA, we proved that TRPM7 mediated both calcium and magnesium changes in cardiac fibroblasts which contribute to fibrosis progress. This study suggested that TRPM7 should play a pivotal role in cardiac fibroblast functions associated to cardiac fibrosis development.
authors.affiliation: Laboratory of Pharmacology and Toxicology, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, Guangdong Province, People's Republic of China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Yu
authors.affiliation: Laboratory of Pharmacology and Toxicology, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, Guangdong Province, People's Republic of China.
authors.forename: Shaorui
authors.initials: S
authors.lastname: Chen
authors.affiliation: Laboratory of Pharmacology and Toxicology, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, Guangdong Province, People's Republic of China.
authors.forename: Chuyao
authors.initials: C
authors.lastname: Xiao
authors.affiliation: Laboratory of Pharmacology and Toxicology, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, Guangdong Province, People's Republic of China.
authors.forename: Yanyan
authors.initials: Y
authors.lastname: Jia
authors.affiliation: Laboratory of Pharmacology and Toxicology, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, Guangdong Province, People's Republic of China.
authors.forename: Jinlei
authors.initials: J
authors.lastname: Guo
authors.affiliation: Laboratory of Pharmacology and Toxicology, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, Guangdong Province, People's Republic of China. Electronic address: lssjjm@mail.sysu.edu.cn.
authors.forename: Jianmin
authors.initials: J
authors.lastname: Jiang
authors.affiliation: Laboratory of Pharmacology and Toxicology, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, Guangdong Province, People's Republic of China. Electronic address: liupq@mail.sysu.edu.cn.
authors.forename: Peiqing
authors.initials: P
authors.lastname: Liu
mesh_terms: D000199:Actins / Q000378:metabolism; D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D001896:Boron Compounds / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D055513:Connective Tissue Growth Factor / Q000378:metabolism; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D005355:Fibrosis / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology; D008274:Magnesium / Q000378:metabolism*; D008297:Male; D050778:NFATC Transcription Factors / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000378:metabolism; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D050053:TRPM Cation Channels / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*
chemical_list: D000199:Actins; D000804:Angiotensin II; D001896:Boron Compounds; D002118:Calcium; D055513:Connective Tissue Growth Factor; D050760:Cyclin-Dependent Kinase Inhibitor p27; D008274:Magnesium; D050778:NFATC Transcription Factors; D009419:Nerve Tissue Proteins; D034741:RNA, Small Interfering; D050053:TRPM Cation Channels; C526316:CCN2 protein, rat; C493962:Cdkn1b protein, rat; C477593:Nfatc4 protein, rat; C498862:Acta2 protein, rat; C109986:2-aminoethoxydiphenyl borate; C486584:Trpm7 protein, rat
keywords: Calcium; Cardiac fibrosis; Magnesium; TRPM7