Transient Receptor Potential Melastatin 7 (TRPM7) Contributes to H2O2-Induced Cardiac Fibrosis via Mediating Ca2+ Influx and Extracellular Signal–Regulated Kinase 1/2 (ERK1/2) Activation in Cardiac Fibroblasts

Guo, Jinchao; Yu, Yang; Jia, Yanyan; Ma, Yunzi; Zhang, Bo-Yu; Liu, Peiqing; Chen, Shao‐Rui; Jiang, Jianmin

doi:10.1254/jphs.13224fp

Cited by 36 publications

(39 citation statements)

References 35 publications

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“…Moreover, it has been shown an up‐regulation of this channel in patients with non‐ischaemic dilated cardiomyopathy with ventricular tachycardias compared with non‐ventricular tachycardia hearts, suggesting an adverse myocardial remodelling in the ventricular tachycardia group . Additionally, experiments on silencing TRPM7 gene (shTRPM7) have demonstrated decrease in the progression of cardiac fibrosis …”

Section: Discussionsupporting

confidence: 73%

“…15 Transient receptor potential melastatin 7 ion channel is responsible for Ca 2+ and Mg 2+ trafficking in fibroblasts, as reported in different studies, being an important modulator of cardiac fibrosis. 10,16 Different pathways activate to promote fibrogenesis, and there is evidence supporting the implication of TRPM7-Ca 2+ mediated current in the activation of TFG-ß1, 7 ERK ½, 8 and Ang II 10,17 pathways. Previous studies have reported an up-regulation of TRPM7 in HF models 12 and the up-regulation of TRPM7-mediated current in atrial fibrillation patients.…”

Section: Discussionmentioning

confidence: 99%

“…It is a divalent cation channel constitutively opened, permeable to Ca 2+ and Mg 2+ . This dual function makes this channel an important regulator of many processes such as cell viability, cytoskeleton organization, magnesium homeostasis and cardiac fibrosis …”

Section: Introductionmentioning

confidence: 99%

“…2 This dual function makes this channel an important regulator of many processes such as cell viability, 3 cytoskeleton organization, 4 magnesium homeostasis 5,6 and cardiac fibrosis. 7,8 Cardiac fibrosis induces an adverse structural remodelling of the myocardium, being a detrimental factor that results in abnormalities in cardiac conduction, loss of contractility, and hardening of ventricular walls, thus contributing to cardiovascular diseases including heart failure (HF). 9 The role of TRPM7 in the fibrotic process has been suggested to occur via the Ca 2+ mediated signals that contribute to TGF-ß1-induced fibrogenesis, 7 through ERK1/2 activation due to phosphorylation and Ca 2+ influx 8 and by regulation of intracellular Ca 2+ and Mg 2+ transport in Angiotensin II stimulation.…”

Section: Introductionmentioning

confidence: 99%

“…7,8 Cardiac fibrosis induces an adverse structural remodelling of the myocardium, being a detrimental factor that results in abnormalities in cardiac conduction, loss of contractility, and hardening of ventricular walls, thus contributing to cardiovascular diseases including heart failure (HF). 9 The role of TRPM7 in the fibrotic process has been suggested to occur via the Ca 2+ mediated signals that contribute to TGF-ß1-induced fibrogenesis, 7 through ERK1/2 activation due to phosphorylation and Ca 2+ influx 8 and by regulation of intracellular Ca 2+ and Mg 2+ transport in Angiotensin II stimulation. 10 A deregulation of TRPM7 channel or current has been previously reported in animal models of HF and in atrial fibrillation patients, 7,11,12 but there are no studies analysing its expression in human ischaemic cardiomyopathy (ICM).…”

Section: Introductionmentioning

confidence: 99%

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TRPM7 is down‐regulated in both left atria and left ventricle of ischaemic cardiomyopathy patients and highly related to changes in ventricular function

Ortega¹,

Roselló‐Lletí²,

Tarazón³

et al. 2016

ESC Heart Failure

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AimsThe kinase ion channel transient receptor potential melastatin 7 (TRPM7) is considered a modulator of cardiac fibrosis progression; nevertheless, we lack of studies analysing its role in human ischaemic cardiomyopathy (ICM). Our objective was to analyse the expression of genes encoding cardiac ion channels in human ICM, focusing on the alterations in mRNA levels of TRPM7 and its relationship with changes in the ventricular function.Methods and resultsRNA‐sequencing was carried out in 13 left ventricular (LV) samples of patients with ICM compared with a control group (n = 10). The analysis revealed a total of 25 ion channel genes differentially expressed. We performed an RTqPCR analysis of the TRPM7 mRNA in LV and left atrial samples and found that it was down‐regulated in both cavities (−1.43‐fold and −1.52‐fold, respectively). Atrial TRPM7 mRNA levels showed an excellent and inverse relationships with the depressed ejection fraction (r = −0.724, P = 0.042) and with the mitral A wave (r = −0.938, P = 0.006).ConclusionsWe report the down‐regulation of TRPM7 in tissue samples from both left atria and left ventricle in patients with ICM. We found an inverse relationship between both cardiac chambers mRNA levels with LV dysfunction, suggesting an important role of TRPM7 in the left atrial and LV functional depression found in this cardiomyopathy.

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Section: Discussionsupporting

confidence: 73%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

TRPM7 is down‐regulated in both left atria and left ventricle of ischaemic cardiomyopathy patients and highly related to changes in ventricular function

Ortega¹,

Roselló‐Lletí²,

Tarazón³

et al. 2016

ESC Heart Failure

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Amine oxidase copper‐containing 3 aggravates cardiac remodelling by generating hydrogen peroxide after myocardial infarction

Zhong

Que

et al. 2023

The Journal of Pathology

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Amine oxidase copper‐containing 3 (AOC3) is a member of the semicarbazide‐sensitive amine oxidase enzyme family. It acts as an ectoenzyme catalysing the oxidative deamination of primary amines and generating hydrogen peroxide (H2O2). While AOC3 is implicated in cardiovascular diseases such as atherosclerosis, its role in cardiac remodelling after myocardial infarction (MI) is unclear. In this study, we first confirmed a long‐term upregulation of AOC3 in both cardiac myofibroblasts after MI in vivo and angiotensin II (ANGII)‐treated cardiac fibroblasts in vitro. AOC3 knockdown not only inhibited the activation of cardiac fibroblasts induced by ANGII but also alleviated cardiac fibrosis in mice after MI. Using sh‐AOC3 lentiviruses, exogenous recombinant AOC3 (r‐AOC3), semicarbazide (an AOC3 inhibitor), and catalase (a hydrogen peroxide scavenger) treatments, we also demonstrated that AOC3 promoted H2O2 generation, increased oxidative stress, and enhanced ERK1/2 activation, which were responsible for the activation of cardiac fibroblasts. In particular, AOC3 knockdown also improved cardiac function and hypertrophy after MI. Through a coculture system, we confirmed that AOC3 expressed on cardiac myofibroblasts was able to enhance oxidative stress and induce hypertrophy of cardiomyocytes by promoting H2O2 generation. Similarly, r‐AOC3 promoted H2O2 generation and resulted in oxidative stress and hypertrophy of cardiomyocytes, which were almost inhibited by both semicarbazide and catalase. In conclusion, AOC3 plays a critical role in cardiac fibrosis and hypertrophy after MI by promoting the generation of H2O2. AOC3 is a promising therapeutic target against cardiac remodelling. © 2023 The Pathological Society of Great Britain and Ireland.

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The Role of Mechanosensitive Signaling Cascades in Repair and Fibrotic Remodeling of the Infarcted Heart

Humeres

Venugopal

Frangogiannis

2023

Cardiac and Vascular Biology

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Transient Receptor Potential Melastatin 7 (TRPM7) Contributes to H2O2-Induced Cardiac Fibrosis via Mediating Ca2+ Influx and Extracellular Signal–Regulated Kinase 1/2 (ERK1/2) Activation in Cardiac Fibroblasts

Cited by 36 publications

References 35 publications

TRPM7 is down‐regulated in both left atria and left ventricle of ischaemic cardiomyopathy patients and highly related to changes in ventricular function

TRPM7 is down‐regulated in both left atria and left ventricle of ischaemic cardiomyopathy patients and highly related to changes in ventricular function

Amine oxidase copper‐containing 3 aggravates cardiac remodelling by generating hydrogen peroxide after myocardial infarction

The Role of Mechanosensitive Signaling Cascades in Repair and Fibrotic Remodeling of the Infarcted Heart

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