Role of TRPM7 in cardiac fibrosis: A potential therapeutic target (Review)

Hu,Feng; Li,Meiyong; Han,Fengyu; Zhang,Qing; Zeng,Yuhao; Zhang,Weifang; Cheng,Xiaoshu

doi:10.3892/etm.2020.9604

Role of TRPM7 in cardiac fibrosis: A potential therapeutic target (Review)

Authors:
- Feng Hu
- Meiyong Li
- Fengyu Han
- Qing Zhang
- Yuhao Zeng
- Weifang Zhang
- Xiaoshu Cheng
View Affiliations

Affiliations: Department of Cardiovascular Medicine, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, P.R. China, Department of Laboratory Medicine, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, P.R. China, Department of Cardiology, The Union Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China, Department of Medical Education, The Second Clinical Medical College of Nanchang University, Nanchang, Jiangxi 330006, P.R. China, Department of Pharmacy, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, P.R. China
Published online on: December 27, 2020 https://doi.org/10.3892/etm.2020.9604
Article Number: 173
Copyright: © Hu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Cardiac fibrosis is a hallmark of cardiac remodeling associated with nearly all forms of heart disease. Clinically, no effective therapeutic drugs aim to inhibit cardiac fibrosis, owing to the complex etiological heterogeneity and pathogenesis of this disease. A two‑in‑one protein structure, a ubiquitous expression profile and unique biophysical characteristics enable the involvement of transient receptor potential melastatin‑subfamily member 7 (TRPM7) in the pathogenesis and development of fibrosis‑related cardiac diseases, such as heart failure (HF), cardiomyopathies, arrhythmia and hyperaldosteronism. In response to a variety of stimuli, multiple bioactive molecules can activate TRPM7 and related signaling pathways, leading to fibroblast proliferation, differentiation and extracellular matrix production in cardiac fibroblasts. TRPM7‑mediated Ca²⁺ signaling and TGF‑β1 signaling pathways are critical for the formation of fibrosis. Accumulating evidence has demonstrated that TRPM7 is a potential pharmacological target for halting the development of fibrotic cardiac diseases. Reliable drug‑like molecules for further development of high‑affinity in vivo drugs targeting TRPM7 are urgently needed. The present review discusses the widespread and significant role of TRPM7 in cardiac fibrosis and focuses on its potential as a therapeutic target for alleviating heart fibrogenesis.

View Figures

View References

1	Weber KT, Sun Y and Díez J: Fibrosis: A living tissue and the infarcted heart. J Am Coll Cardiol. 52:2029–2031. 2008.PubMed/NCBI View Article : Google Scholar
2	Khan R and Sheppard R: Fibrosis in heart disease: Understanding the role of transforming growth factor-beta in cardiomyopathy, valvular disease and arrhythmia. Immunology. 118:10–24. 2006.PubMed/NCBI View Article : Google Scholar
3	Klesen A, Jakob D, Emig R, Kohl P, Ravens U and Peyronnet R: Cardiac fibroblasts: Active players in (atrial) electrophysiology? Herzschrittmacherther Elektrophysiol. 29:62–69. 2018.PubMed/NCBI View Article : Google Scholar
4	Sontia B, Montezano AC, Paravicini T, Tabet F and Touyz RM: Downregulation of renal TRPM7 and increased inflammation and fibrosis in aldosterone-infused mice: Effects of magnesium. Hypertension. 51:915–921. 2008.PubMed/NCBI View Article : Google Scholar
5	Leask A: Getting to the heart of the matter: New insights into cardiac fibrosis. Circ Res. 116:1269–1276. 2015.PubMed/NCBI View Article : Google Scholar
6	Liu J, Zhuang T, Pi J, Chen X, Zhang Q, Li Y, Wang H, Shen Y, Tomlinson B, Chan P, et al: Endothelial Forkhead Box Transcription Factor P1 Regulates Pathological Cardiac Remodeling Through Transforming Growth Factor-β1-Endothelin-1 Signal Pathway. Circulation. 140:665–680. 2019.PubMed/NCBI View Article : Google Scholar
7	Frangogiannis NG: Fibroblasts and the extracellular matrix in right ventricular disease. Cardiovasc Res. 113:1453–1464. 2017.PubMed/NCBI View Article : Google Scholar
8	Travers JG, Kamal FA, Robbins J, Yutzey KE and Blaxall BC: Cardiac Fibrosis: The Fibroblast Awakens. Circ Res. 118:1021–1040. 2016.PubMed/NCBI View Article : Google Scholar
9	Moore-Morris T, Guimarães-Camboa N, Banerjee I, Zambon AC, Kisseleva T, Velayoudon A, Stallcup WB, Gu Y, Dalton ND, Cedenilla M, et al: Resident fibroblast lineages mediate pressure overload-induced cardiac fibrosis. J Clin Invest. 124:2921–2934. 2014.PubMed/NCBI View Article : Google Scholar
10	Zeisberg EM, Tarnavski O, Zeisberg M, Dorfman AL, McMullen JR, Gustafsson E, Chandraker A, Yuan X, Pu WT, Roberts AB, et al: Endothelial-to-mesenchymal transition contributes to cardiac fibrosis. Nat Med. 13:952–961. 2007.PubMed/NCBI View Article : Google Scholar
11	Quijada P, Trembley MA and Small EM: The Role of the Epicardium During Heart Development and Repair. Circ Res. 126:377–394. 2020.PubMed/NCBI View Article : Google Scholar
12	Simões FC, Cahill TJ, Kenyon A, Gavriouchkina D, Vieira JM, Sun X, Pezzolla D, Ravaud C, Masmanian E, Weinberger M, et al: Macrophages directly contribute collagen to scar formation during zebrafish heart regeneration and mouse heart repair. Nat Commun. 11(600)2020.PubMed/NCBI View Article : Google Scholar
13	Sundberg C, Ivarsson M, Gerdin B and Rubin K: Pericytes as collagen-producing cells in excessive dermal scarring. Lab Invest. 74:452–466. 1996.PubMed/NCBI
14	Samanta A, Hughes TET and Moiseenkova-Bell VY: Transient Receptor Potential (TRP) Channels. Subcell Biochem. 87:141–165. 2018.PubMed/NCBI View Article : Google Scholar
15	Kraft R and Harteneck C: The mammalian melastatin-related transient receptor potential cation channels: An overview. Pflugers Arch. 451:204–211. 2005.PubMed/NCBI View Article : Google Scholar
16	Clark K, Middelbeek J, Morrice NA, Figdor CG, Lasonder E and van Leeuwen FN: Massive autophosphorylation of the Ser/Thr-rich domain controls protein kinase activity of TRPM6 and TRPM7. PLoS One. 3(e1876)2008.PubMed/NCBI View Article : Google Scholar
17	Li M, Jiang J and Yue L: Functional characterization of homo- and heteromeric channel kinases TRPM6 and TRPM7. J Gen Physiol. 127:525–537. 2006.PubMed/NCBI View Article : Google Scholar
18	Zhang Z, Yu H, Huang J, Faouzi M, Schmitz C, Penner R and Fleig A: The TRPM6 kinase domain determines the Mg·ATP sensitivity of TRPM7/M6 heteromeric ion channels. J Biol Chem. 289:5217–5227. 2014.PubMed/NCBI View Article : Google Scholar
19	Hofmann T, Chubanov V, Gudermann T and Montell C: TRPM5 is a voltage-modulated and Ca(²⁺)-activated monovalent selective cation channel. Curr Biol. 13:1153–1158. 2003.PubMed/NCBI View Article : Google Scholar
20	Fonfria E, Murdock PR, Cusdin FS, Benham CD, Kelsell RE and McNulty S: Tissue distribution profiles of the human TRPM cation channel family. J Recept Signal Transduct Res. 26:159–178. 2006.PubMed/NCBI View Article : Google Scholar
21	Yue Z, Zhang Y, Xie J, Jiang J and Yue L: Transient receptor potential (TRP) channels and cardiac fibrosis. Curr Top Med Chem. 13:270–282. 2013.PubMed/NCBI View Article : Google Scholar
22	Rios FJ, Zou ZG, Harvey AP, Harvey KY, Nosalski R, Anyfanti P, Camargo LL, Lacchini S, Ryazanov AG, Ryazanova L, et al: Chanzyme TRPM7 protects against cardiovascular inflammation and fibrosis. Cardiovasc Res. 116:721–735. 2020.PubMed/NCBI View Article : Google Scholar
23	Antunes TT, Callera GE, He Y, Yogi A, Ryazanov AG, Ryazanova LV, Zhai A, Stewart DJ, Shrier A and Touyz RM: Transient Receptor Potential Melastatin 7 Cation Channel Kinase: New Player in Angiotensin II-Induced Hypertension. Hypertension. 67:763–773. 2016.PubMed/NCBI View Article : Google Scholar
24	Clapham DE: TRP channels as cellular sensors. Nature. 426:517–524. 2003.PubMed/NCBI View Article : Google Scholar
25	Duan J, Li Z, Li J, Hulse RE, Santa-Cruz A, Valinsky WC, Abiria SA, Krapivinsky G, Zhang J and Clapham DE: Structure of the mammalian TRPM7, a magnesium channel required during embryonic development. Proc Natl Acad Sci USA. 115:E8201–E8210. 2018.PubMed/NCBI View Article : Google Scholar
26	Zou ZG, Rios FJ, Montezano AC and Touyz RM: TRPM7, Magnesium, and Signaling. Int J Mol Sci. 20(1877)2019.PubMed/NCBI View Article : Google Scholar
27	Suzuki S, Lis A, Schmitz C, Penner R and Fleig A: The TRPM7 kinase limits receptor-induced calcium release by regulating heterotrimeric G-proteins. Cell Mol Life Sci. 75:3069–3078. 2018.PubMed/NCBI View Article : Google Scholar
28	Nadolni W and Zierler S: The Channel-Kinase TRPM7 as Novel Regulator of Immune System Homeostasis. Cells. 7(109)2018.PubMed/NCBI View Article : Google Scholar
29	Sah R, Mesirca P, Mason X, Gibson W, Bates-Withers C, Van den Boogert M, Chaudhuri D, Pu WT, Mangoni ME and Clapham DE: Timing of myocardial trpm7 deletion during cardiogenesis variably disrupts adult ventricular function, conduction, and repolarization. Circulation. 128:101–114. 2013.PubMed/NCBI View Article : Google Scholar
30	Huang Y, Leng TD, Inoue K, Yang T, Liu M, Horgen FD, Fleig A, Li J and Xiong ZG: TRPM7 channels play a role in high glucose-induced endoplasmic reticulum stress and neuronal cell apoptosis. J Biol Chem. 293:14393–14406. 2018.PubMed/NCBI View Article : Google Scholar
31	Chiang YF, Chen HY, Lee IT, Chien LS, Huang JH, Kolisek M, Cheng FC and Tsai SW: Magnesium-responsive genes are downregulated in diabetic patients after a three-month exercise program on a bicycle ergometer. J Chin Med Assoc. 82:495–499. 2019.PubMed/NCBI View Article : Google Scholar
32	Sun HS: Role of TRPM7 in cerebral ischaemia and hypoxia. J Physiol. 595:3077–3083. 2017.PubMed/NCBI View Article : Google Scholar
33	Chen M, Zhang W, Shi J and Jiang S: TGF-β1-Induced Airway Smooth Muscle Cell Proliferation Involves TRPM7-Dependent Calcium Influx via TGFβR/SMAD3. Mol Immunol. 103:173–181. 2018.PubMed/NCBI View Article : Google Scholar
34	Voringer S, Schreyer L, Nadolni W, Meier MA, Woerther K, Mittermeier C, Ferioli S, Singer S, Holzer K, Zierler S, et al: Inhibition of TRPM7 blocks MRTF/SRF-dependent transcriptional and tumorigenic activity. Oncogene. 39:2328–2344. 2020.PubMed/NCBI View Article : Google Scholar
35	Yee NS: Role of TRPM7 in Cancer: Potential as Molecular Biomarker and Therapeutic Target. Pharmaceuticals (Basel). 10(39)2017.PubMed/NCBI View Article : Google Scholar
36	Lal N, Bhardwaj S, Lalgudi Ganesan S, Sharma R and Jain P: Case of hypomagnesemia with secondary hypocalcemia with a novel TRPM6 mutation. Neurol India. 66:1795–1800. 2018.PubMed/NCBI View Article : Google Scholar
37	Ryazanova LV, Rondon LJ, Zierler S, Hu Z, Galli J, Yamaguchi TP, Mazur A, Fleig A and Ryazanov AG: TRPM7 is essential for Mg(²⁺) homeostasis in mammals. Nat Commun. 1(109)2010.PubMed/NCBI View Article : Google Scholar
38	Wang Y, Chen L, Wang K, Da Y, Zhou M, Yan H, Zheng D, Zhong S, Cai S, Zhu H, et al: Suppression of TRPM2 reduces renal fibrosis and inflammation through blocking TGF-β1-regulated JNK activation. Biomed Pharmacother. 120(109556)2019.PubMed/NCBI View Article : Google Scholar
39	Nadler MJ, Hermosura MC, Inabe K, Perraud AL, Zhu Q, Stokes AJ, Kurosaki T, Kinet JP, Penner R, Scharenberg AM, et al: LTRPC7 is a Mg.ATP-regulated divalent cation channel required for cell viability. Nature. 411:590–595. 2001.PubMed/NCBI View Article : Google Scholar
40	Chokshi R, Matsushita M and Kozak JA: Sensitivity of TRPM7 channels to Mg²⁺ characterized in cellfree patches of Jurkat T lymphocytes. Am J Physiol Cell Physiol. 302:C1642–C1651. 2012.PubMed/NCBI View Article : Google Scholar
41	Runnels LW, Yue L and Clapham DE: The TRPM7 channel is inactivated by PIP(2) hydrolysis. Nat Cell Biol. 4:329–336. 2002.PubMed/NCBI View Article : Google Scholar
42	Deason-Towne F, Perraud AL and Schmitz C: Identification of Ser/Thr phosphorylation sites in the C2-domain of phospholipase C γ2 (PLCγ2) using TRPM7-kinase. Cell Signal. 24:2070–2075. 2012.PubMed/NCBI View Article : Google Scholar
43	Abiria SA, Krapivinsky G, Sah R, Santa-Cruz AG, Chaudhuri D, Zhang J, Adstamongkonkul P, DeCaen PG and Clapham DE: TRPM7 senses oxidative stress to release Zn²⁺ from unique intracellular vesicles. Proc Natl Acad Sci USA. 114:E6079–E6088. 2017.PubMed/NCBI View Article : Google Scholar
44	Clark K, Langeslag M, van Leeuwen B, Ran L, Ryazanov AG, Figdor CG, Moolenaar WH, Jalink K and van Leeuwen FN: TRPM7, a novel regulator of actomyosin contractility and cell adhesion. EMBO J. 25:290–301. 2006.PubMed/NCBI View Article : Google Scholar
45	Clark K, Middelbeek J, Dorovkov MV, Figdor CG, Ryazanov AG, Lasonder E and van Leeuwen FN: The alpha-kinases TRPM6 and TRPM7, but not eEF-2 kinase, phosphorylate the assembly domain of myosin IIA, IIB and IIC. FEBS Lett. 582:2993–2997. 2008.PubMed/NCBI View Article : Google Scholar
46	Clark K, Middelbeek J, Lasonder E, Dulyaninova NG, Morrice NA, Ryazanov AG, Bresnick AR, Figdor CG and van Leeuwen FN: TRPM7 regulates myosin IIA filament stability and protein localization by heavy chain phosphorylation. J Mol Biol. 378:790–803. 2008.PubMed/NCBI View Article : Google Scholar
47	Dorovkov MV and Ryazanov AG: Phosphorylation of annexin I by TRPM7 channel-kinase. J Biol Chem. 279:50643–50646. 2004.PubMed/NCBI View Article : Google Scholar
48	Dorovkov MV, Kostyukova AS and Ryazanov AG: Phosphorylation of annexin A1 by TRPM7 kinase: A switch regulating the induction of an α-helix. Biochemistry. 50:2187–2193. 2011.PubMed/NCBI View Article : Google Scholar
49	Krapivinsky G, Krapivinsky L, Manasian Y and Clapham DE: The TRPM7 chanzyme is cleaved to release a chromatin-modifying kinase. Cell. 157:1061–1072. 2014.PubMed/NCBI View Article : Google Scholar
50	Ryazanova LV, Dorovkov MV, Ansari A and Ryazanov AG: Characterization of the protein kinase activity of TRPM7/ChaK1, a protein kinase fused to the transient receptor potential ion channel. J Biol Chem. 279:3708–3716. 2004.PubMed/NCBI View Article : Google Scholar
51	Matsushita M, Kozak JA, Shimizu Y, McLachlin DT, Yamaguchi H, Wei FY, Tomizawa K, Matsui H, Chait BT, Cahalan MD, et al: Channel function is dissociated from the intrinsic kinase activity and autophosphorylation of TRPM7/ChaK1. J Biol Chem. 280:20793–20803. 2005.PubMed/NCBI View Article : Google Scholar
52	Desai BN, Krapivinsky G, Navarro B, Krapivinsky L, Carter BC, Febvay S, Delling M, Penumaka A, Ramsey IS, Manasian Y, et al: Cleavage of TRPM7 releases the kinase domain from the ion channel and regulates its participation in Fas-induced apoptosis. Dev Cell. 22:1149–1162. 2012.PubMed/NCBI View Article : Google Scholar
53	Yu Y, Chen S, Xiao C, Jia Y, Guo J, Jiang J and Liu P: TRPM7 is involved in angiotensin II induced cardiac fibrosis development by mediating calcium and magnesium influx. Cell Calcium. 55:252–260. 2014.PubMed/NCBI View Article : Google Scholar
54	Song C, Bae Y, Jun J, Lee H, Kim ND, Lee KB, Hur W, Park JY and Sim T: Identification of TG100-115 as a new and potent TRPM7 kinase inhibitor, which suppresses breast cancer cell migration and invasion. Biochim Biophys Acta Gen Subj. 1861:947–957. 2017.PubMed/NCBI View Article : Google Scholar
55	Yang CW, Liu H, Li XD, Sui SG and Liu YF: Salvianolic acid B protects against acute lung injury by decreasing TRPM6 and TRPM7 expressions in a rat model of sepsis. J Cell Biochem. 119:701–711. 2018.PubMed/NCBI View Article : Google Scholar
56	Liu A, Wu J, Yang C, Wu Y, Zhang Y, Zhao F, Wang H, Yuan L, Song L, Zhu T, et al: TRPM7 in CHBP-induced renoprotection upon ischemia reperfusion-related injury. Sci Rep. 8(5510)2018.PubMed/NCBI View Article : Google Scholar
57	Al Hattab D and Czubryt MP: A primer on current progress in cardiac fibrosis. Can J Physiol Pharmacol. 95:1091–1099. 2017.PubMed/NCBI View Article : Google Scholar
58	Jalife J and Kaur K: Atrial remodeling, fibrosis, and atrial fibrillation. Trends Cardiovasc Med. 25:475–484. 2015.PubMed/NCBI View Article : Google Scholar
59	Schirone L, Forte M, Palmerio S, Yee D, Nocella C, Angelini F, Pagano F, Schiavon S, Bordin A, Carrizzo A, et al: A Review of the Molecular Mechanisms Underlying the Development and Progression of Cardiac Remodeling. Oxid Med Cell Longev. 2017(3920195)2017.PubMed/NCBI View Article : Google Scholar
60	Yue L, Xie J and Nattel S: Molecular determinants of cardiac fibroblast electrical function and therapeutic implications for atrial fibrillation. Cardiovasc Res. 89:744–753. 2011.PubMed/NCBI View Article : Google Scholar
61	Zhang YH, Sun HY, Chen KH, Du XL, Liu B, Cheng LC, Li X, Jin MW and Li GR: Evidence for functional expression of TRPM7 channels in human atrial myocytes. Basic Res Cardiol. 107(282)2012.PubMed/NCBI View Article : Google Scholar
62	González A, López B and Díez J: Fibrosis in hypertensive heart disease: Role of the renin-angiotensin-aldosterone system. Med Clin North Am. 88:83–97. 2004.PubMed/NCBI View Article : Google Scholar
63	Olson ER, Shamhart PE, Naugle JE and Meszaros JG: Angiotensin II-induced extracellular signal-regulated kinase 1/2 activation is mediated by protein kinase Cdelta and intracellular calcium in adult rat cardiac fibroblasts. Hypertension. 51:704–711. 2008.PubMed/NCBI View Article : Google Scholar
64	Manabe I, Shindo T and Nagai R: Gene expression in fibroblasts and fibrosis: Involvement in cardiac hypertrophy. Circ Res. 91:1103–1113. 2002.PubMed/NCBI View Article : Google Scholar
65	Parekh AB: Calcium signalling in health and disease. Semin Cell Dev Biol. 94:1–2. 2019.PubMed/NCBI View Article : Google Scholar
66	Fan D, Takawale A, Lee J and Kassiri Z: Cardiac fibroblasts, fibrosis and extracellular matrix remodeling in heart disease. Fibrogenesis Tissue Repair. 5(15)2012.PubMed/NCBI View Article : Google Scholar
67	Du J, Xie J, Zhang Z, Tsujikawa H, Fusco D, Silverman D, Liang B and Yue L: TRPM7-mediated Ca²⁺ signals confer fibrogenesis in human atrial fibrillation. Circ Res. 106:992–1003. 2010.PubMed/NCBI View Article : Google Scholar
68	Wu Y, Liu Y, Pan Y, Lu C, Xu H, Wang X, Liu T, Feng K and Tang Y: MicroRNA-135a inhibits cardiac fibrosis induced by isoproterenol via TRPM7 channel. Biomed Pharmacother. 104:252–260. 2018.PubMed/NCBI View Article : Google Scholar
69	Dragún M, Gažová A, Kyselovič J, Hulman M and Máťuš M: TRP Channels Expression Profile in Human End-Stage Heart Failure. Medicina (Kaunas). 55(380)2019.PubMed/NCBI View Article : Google Scholar
70	Morgan JP, Erny RE, Allen PD, Grossman W and Gwathmey JK: Abnormal intracellular calcium handling, a major cause of systolic and diastolic dysfunction in ventricular myocardium from patients with heart failure. Circulation. 81:121–132. 1990.PubMed/NCBI
71	Altura BM, Kostellow AB, Zhang A, Li W, Morrill GA, Gupta RK and Altura BT: Expression of the nuclear factor-kappaB and proto-oncogenes c-fos and c-jun are induced by low extracellular Mg²⁺ in aortic and cerebral vascular smooth muscle cells: Possible links to hypertension, atherogenesis, and stroke. Am J Hypertens. 16:701–707. 2003.
72	Touyz RM and Yao G: Up-regulation of vascular and renal mitogen-activated protein kinases in hypertensive rats is normalized by inhibitors of the Na⁺/Mg²⁺ exchanger. Clin Sci (Lond). 105:235–242. 2003.PubMed/NCBI View Article : Google Scholar
73	Baldoli E and Maier JA: Silencing TRPM7 mimics the effects of magnesium deficiency in human microvascular endothelial cells. Angiogenesis. 15:47–57. 2012.PubMed/NCBI View Article : Google Scholar
74	Bates-Withers C and Sah RandClapham DE: TRPM7, the Mg(²⁺) inhibited channel and kinase. Adv Exp Med Biol. 704:173–183. 2011.PubMed/NCBI View Article : Google Scholar
75	Montezano AC, Zimmerman D, Yusuf H, Burger D, Chignalia AZ, Wadhera V, van Leeuwen FN and Touyz RM: Vascular smooth muscle cell differentiation to an osteogenic phenotype involves TRPM7 modulation by magnesium. Hypertension. 56:453–462. 2010.PubMed/NCBI View Article : Google Scholar
76	Schiffrin EL and Touyz RM: Calcium, magnesium, and oxidative stress in hyperaldosteronism. Circulation. 111:830–831. 2005.PubMed/NCBI View Article : Google Scholar
77	Miller BA and Zhang W: TRP channels as mediators of oxidative stress. Adv Exp Med Biol. 704:531–544. 2011.PubMed/NCBI View Article : Google Scholar
78	Sun Y: Myocardial repair/remodelling following infarction: Roles of local factors. Cardiovasc Res. 81:482–490. 2009.PubMed/NCBI View Article : Google Scholar
79	Swynghedauw B: Molecular mechanisms of myocardial remodeling. Physiol Rev. 79:215–262. 1999.PubMed/NCBI View Article : Google Scholar
80	Parajuli N, Valtuille L, Basu R, Famulski KS, Halloran PF, Sergi C and Oudit GY: Determinants of ventricular arrhythmias in human explanted hearts with dilated cardiomyopathy. Eur J Clin Invest. 45:1286–1296. 2015.PubMed/NCBI View Article : Google Scholar
81	Demir T, Yumrutas O, Cengiz B, Demiryurek S, Unverdi H, Kaplan DS, Bayraktar R, Ozkul N and Bagcı C: Evaluation of TRPM (transient receptor potential melastatin) genes expressions in myocardial ischemia and reperfusion. Mol Biol Rep. 41:2845–2849. 2014.PubMed/NCBI View Article : Google Scholar
82	Ortega A, Roselló-Lletí E, Tarazón E, Gil-Cayuela C, Lago F, González-Juanatey JR, Martinez-Dolz L, Portolés M and Rivera M: TRPM7 is down-regulated in both left atria and left ventricle of ischaemic cardiomyopathy patients and highly related to changes in ventricular function. ESC Heart Fail. 3:220–224. 2016.PubMed/NCBI View Article : Google Scholar
83	Guo JL, Yu Y, Jia YY, Ma YZ, Zhang BY, Liu PQ, Chen SR and Jiang JM: Transient receptor potential melastatin 7 (TRPM7) contributes to H₂O₂-induced cardiac fibrosis via mediating Ca(²⁺) influx and extracellular signal-regulated kinase 1/2 (ERK1/2) activation in cardiac fibroblasts. J Pharmacol Sci. 125:184–192. 2014.PubMed/NCBI View Article : Google Scholar
84	Wei Y, Wu Y, Feng K, Zhao Y, Tao R, Xu H and Tang Y: Astragaloside IV inhibits cardiac fibrosis via miR-135a-TRPM7-TGF-β/Smads pathway. J Ethnopharmacol. 249(112404)2020.PubMed/NCBI View Article : Google Scholar
85	Lu J, Wang QY, Zhou Y, Lu XC, Liu YH, Wu Y, Guo Q, Ma YT and Tang YQ: AstragalosideIV against cardiac fibrosis by inhibiting TRPM7 channel. Phytomedicine. 30:10–17. 2017.PubMed/NCBI View Article : Google Scholar
86	Olson ER, Shamhart PE, Naugle JE and Meszaros JG: Angiotensin II-induced extracellular signal-regulated kinase 1/2 activation is mediated by protein kinase Cdelta and intracellular calcium in adult rat cardiac fibroblasts. Hypertension. 51:704–711. 2008.PubMed/NCBI View Article : Google Scholar
87	Li S, Li M, Yi X, Guo F, Zhou Y, Chen S and Wu X: TRPM7 channels mediate the functional changes in cardiac fibroblasts induced by angiotensin II. Int J Mol Med. 39:1291–1298. 2017.PubMed/NCBI View Article : Google Scholar
88	Zhou Y, Yi X, Wang T and Li M: Effects of angiotensin II on transient receptor potential melastatin 7 channel function in cardiac fibroblasts. Exp Ther Med. 9:2008–2012. 2015.PubMed/NCBI View Article : Google Scholar
89	Zhong H, Wang T, Lian G, Xu C, Wang H and Xie L: TRPM7 regulates angiotensin II-induced sinoatrial node fibrosis in sick sinus syndrome rats by mediating Smad signaling. Heart Vessels. 33:1094–1105. 2018.PubMed/NCBI View Article : Google Scholar
90	Xu F, Liu C, Zhou D and Zhang L: TGF-β/SMAD Pathway and Its Regulation in Hepatic Fibrosis. J Histochem Cytochem. 64:157–167. 2016.PubMed/NCBI View Article : Google Scholar
91	Liu KH, Zhou N, Zou Y, Yang YY, OuYang SX and Liang YM: Spleen Tyrosine Kinase (SYK) in the Progression of Peritoneal Fibrosis Through Activation of the TGF-β1/Smad3 Signaling Pathway. Med Sci Monit. 25:9346–9356. 2019.PubMed/NCBI View Article : Google Scholar
92	Penke LR and Peters-Golden M: Molecular determinants of mesenchymal cell activation in fibroproliferative diseases. Cell Mol Life Sci. 76:4179–4201. 2019.PubMed/NCBI View Article : Google Scholar
93	Overstreet JM, Samarakoon R, Meldrum KK and Higgins PJ: Redox control of p53 in the transcriptional regulation of TGF-β1 target genes through SMAD cooperativity. Cell Signal. 26:1427–1436. 2014.PubMed/NCBI View Article : Google Scholar
94	Yu M, Huang C, Huang Y, Wu X, Li X and Li J: Inhibition of TRPM7 channels prevents proliferation and differentiation of human lung fibroblasts. Inflamm Res. 62:961–970. 2013.PubMed/NCBI View Article : Google Scholar
95	Chubanov V, Ferioli S and Gudermann T: Assessment of TRPM7 functions by drug-like small molecules. Cell Calcium. 67:166–173. 2017.PubMed/NCBI View Article : Google Scholar
96	Hofmann T, Schäfer S, Linseisen M, Sytik L, Gudermann T and Chubanov V: Activation of TRPM7 channels by small molecules under physiological conditions. Pflugers Arch. 466:2177–2189. 2014.PubMed/NCBI View Article : Google Scholar
97	Schäfer S, Ferioli S, Hofmann T, Zierler S, Gudermann T and Chubanov V: Mibefradil represents a new class of benzimidazole TRPM7 channel agonists. Pflugers Arch. 468:623–634. 2016.PubMed/NCBI View Article : Google Scholar
98	Tanai E and Frantz S: Pathophysiology of Heart Failure. Compr Physiol. 6:187–214. 2015.PubMed/NCBI View Article : Google Scholar