TRPM2 channels in alveolar epithelial cells mediate bleomycin-induced lung inflammation

Yonezawa, Ryo; Yamamoto, Shinichiro; Takenaka, Miki; Kage, Yukiko; Negoro, Takaharu; Toda, Takahiro; Ohbayashi, Masayuki; Numata, Tomohiro; Nakano, Yasuko; Yamamoto, Toshinori; Mori, Yasuo; Ishii, Masakazu; Shimizu, Shunichi

doi:10.1016/j.freeradbiomed.2015.11.021

Cited by 26 publications

(18 citation statements)

References 49 publications

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“…Human cardiac fibroblasts (Chatelier et al, 2012;Koivumaki et al, 2014;Li et al, 2009;Zhan et al, 2016) Voltage-gated K + channels Transient outward K + current, I to Delayed rectified K + currents: I K , I Kf Human and rat cardiac fibroblast Rook et al, 1992; Neonatal rat cardiac fibroblasts (Rook et al, 1992;Walsh & Zhang, 2008) Inward-rectifier K + channels K ir , IK v Human lung fibroblasts (Roach et al, 2013) Human cardiac fibroblasts (Aguilar et al, 2014;Li et al, 2009) Canine atrial fibroblasts (Benamer et al, 2009) ATP-activated K + channels K ATP Rat ventricular fibroblasts (Benamer et al, 2009) Human dermal fibroblasts (Bednarczyk et al, 2018) TRP channels TRPA1, TRPC1, TRPC3, TRPC4, TRPC6, TRPV4, TRPM2, TRPM7 Human and mouse lung fibroblasts (Hofmann et al, 2017;Rahaman et al, 2014;Wei et al, 2009;Yonezawa et al, 2016) Mouse proximal tubular cells (Mannaa et al, 2018) Human and rat hepatic stellate cells (Song et al, 2014) Human, rat, and mouse kidney fibroblasts (Saliba et al, 2015) Rat ventricular fibroblasts (Rose et al, 2007) Human, rat, and mouse cardiac fibroblasts (Chen et al, 2010;Du et al, 2010;Li et al, 2019;Mannaa et al, 2018;Oguri et al, 2014;Rahaman et al, 2014;Runnels et al, 2002;Saliba et al, 2015;Song et al, 2014) Cl − channels I Cl-swell , ClC-3, I Cl Human cardiac fibroblasts (Li et al, 2009;…”

Section: Types Of Ion Channels Names Of Ion Channels Cell Types Exprementioning

confidence: 99%

“…Human and mouse lung fibroblasts (Hofmann et al, 2017; Rahaman et al, 2014; Wei et al, 2009; Yonezawa et al, 2016)…”

Section: Introductionmentioning

confidence: 99%

“…TRPC6 has been implicated in cardiac wound healing through myofibroblast transdifferentiation (Davis et al, ). In model lung fibrosis, TRPM2 contributed to bleomycin‐induced lung inflammation (Yonezawa et al, ), TRPC6 contributed to TGF‐β1‐induced myofibroblast differentiation during fibrosis (Hofmann et al, ) and TRPV4 activity mediated pulmonary fibrosis through the regulation of myofibroblast differentiation (Rahaman et al, ). TRPC3 channels were central in renal fibroblast proliferation, differentiation and activation through Ca 2+ ‐mediated ERK signalling, suggesting that TRPC3 inhibitors could significantly improve renal remodelling in kidney disease (Saliba et al, ).…”

Section: Introductionmentioning

confidence: 99%

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Ca²⁺ signalling in fibroblasts and the therapeutic potential of K_Ca3.1 channel blockers in fibrotic diseases

Roach

Bradding

2020

British J Pharmacology

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The role of Ca2+ signalling in fibroblasts is of great interest in fibrosis‐related diseases. Intracellular free Ca2+ ([Ca2+]i) is a ubiquitous secondary messenger, regulating a number of cellular functions such as secretion, metabolism, differentiation, proliferation and contraction. The intermediate conductance Ca2+‐activated K+ channel KCa3.1 is pivotal in Ca2+ signalling and plays a central role in fibroblast processes including cell activation, migration and proliferation through the regulation of cell membrane potential. Evidence from a number of approaches demonstrates that KCa3.1 plays an important role in the development of many fibrotic diseases, including idiopathic pulmonary, renal tubulointerstitial fibrosis and cardiovascular disease. The KCa3.1 selective blocker senicapoc was well tolerated in clinical trials for sickle cell disease, raising the possibility of rapid translation to the clinic for people suffering from pathological fibrosis. This review after analysing all the data, concludes that targeting KCa3.1 should be a high priority for human fibrotic disease.

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Section: Types Of Ion Channels Names Of Ion Channels Cell Types Exprementioning

confidence: 99%

“…Human and mouse lung fibroblasts (Hofmann et al, 2017; Rahaman et al, 2014; Wei et al, 2009; Yonezawa et al, 2016)…”

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Ca²⁺ signalling in fibroblasts and the therapeutic potential of K_Ca3.1 channel blockers in fibrotic diseases

Roach

Bradding

2020

British J Pharmacology

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“…TRPM2 in alveolar epithelial cells plays an important role in bleomycin-induced lung injury [ 85 ]. Bleomycin is a glycopeptide antibiotic with potent antitumor activity.…”

Section: Ros-coupled Diseases and Trpm2mentioning

confidence: 99%

“…In vitro, activation by LPS of TRPM2 in monocytes and cultured microglia is involved in the generation of inflammatory cytokines [ 40 , 84 , 86 ]. By contrast, in vivo studies found no difference between WT and Trpm2 KO mice in the secretion of inflammatory cytokines and the infiltration of inflammatory cells into the lungs following LPS administration [ 85 , 87 ]. Therefore, other signaling pathways (e.g., TLR4-mediated signaling) rather than Ca 2+ signaling via TRPM2 may play a pivotal role in LPS-induced lung inflammation in vivo.…”

Section: Ros-coupled Diseases and Trpm2mentioning

confidence: 99%

Targeting TRPM2 in ROS-Coupled Diseases

Yamamoto

Shimizu

2016

Pharmaceuticals

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Under pathological conditions such as inflammation and ischemia-reperfusion injury large amounts of reactive oxygen species (ROS) are generated which, in return, contribute to the development and exacerbation of disease. The second member of the transient receptor potential (TRP) melastatin subfamily, TRPM2, is a Ca2+-permeable non-selective cation channel, activated by ROS in an ADP-ribose mediated fashion. In other words, TRPM2 functions as a transducer that converts oxidative stress into Ca2+ signaling. There is good evidence that TRPM2 plays an important role in ROS-coupled diseases. For example, in monocytes the influx of Ca2+ through TRPM2 activated by ROS contributes to the aggravation of inflammation via chemokine production. In this review, the focus is on TRPM2 as a molecular linker between ROS and Ca2+ signaling in ROS-coupled diseases.

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TRPM2 knockdown attenuates myocardial apoptosis and promotes autophagy in HFD/STZ-induced diabetic mice via regulating the MEK/ERK and mTORC1 signaling pathway

Hu,

Lin

2024

Mol Cell Biochem

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Diabetic cardiomyopathy (DCM) is a major complication of diabetes. Transient receptor potential melastatin 2 (TRPM2) activity increases in diabetic oxidative stress state, and it is involved in myocardial damage and repair. We explore the protective effect of TRPM2 knockdown on the progression of DCM. A type 2 diabetes animal model was established in C57BL/6N mice by long-term high-fat diet (HFD) feeding combined with a single injection of 100-mg/kg streptozotocin (STZ). Genetic knockdown of TRPM2 in heart was accomplished by the intravenous injection via the tail vein of adeno-associated virus type 9 carrying TRPM2 shRNA. Neonatal rat ventricular myocytes was exposed to 45 mM of high-glucose (HG) stimulation for 72 h in vitro to mimic the in vivo conditions. Western blot, real-time quantitative PCR (RT-qPCR), immunohistochemistry and fluorescence, electron, CCK-8, and flow cytometry were used to evaluate the phenotype of cardiac inflammation, fibrosis, apoptosis, and autophagy. Mice with HFD/STZ-induced diabetes exhibited systolic and diastolic dysfunction, as demonstrated by increased myocardial apoptosis and autophagy inhibition in the heart. Compared to control group, the protein expression of TRPM2, bax, cleaved caspase-3, and P62 was significantly elevated, and the protein expression of bcl-2 and LC3-II was significantly decreased in the myocardial tissues of the HFD/STZ-induced diabetes group. Knockdown of TRPM2 significantly reversed the HFD/STZ-induced myocardial apoptosis and autophagy inhibition. TRPM2 silencing attenuated HG-induced apoptosis and autophagy inhibition in primary cardiomyocytes via regulating the MEK/ERK mTORC1 signaling pathway. TRPM2 knockdown attenuates hyperglycemia-induced myocardial apoptosis and promotes autophagy in HFD/STZ-induced diabetic mice or HG-stimulated cardiomyocytes via regulating the MEK/ERK and mTORC1 signaling pathway.

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TRPM2 channels in alveolar epithelial cells mediate bleomycin-induced lung inflammation

Cited by 26 publications

References 49 publications

Ca²⁺ signalling in fibroblasts and the therapeutic potential of K_Ca3.1 channel blockers in fibrotic diseases

Ca²⁺ signalling in fibroblasts and the therapeutic potential of K_Ca3.1 channel blockers in fibrotic diseases

Targeting TRPM2 in ROS-Coupled Diseases

TRPM2 knockdown attenuates myocardial apoptosis and promotes autophagy in HFD/STZ-induced diabetic mice via regulating the MEK/ERK and mTORC1 signaling pathway

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TRPM2 channels in alveolar epithelial cells mediate bleomycin-induced lung inflammation

Cited by 26 publications

References 49 publications

Ca2+ signalling in fibroblasts and the therapeutic potential of KCa3.1 channel blockers in fibrotic diseases

Ca2+ signalling in fibroblasts and the therapeutic potential of KCa3.1 channel blockers in fibrotic diseases

Targeting TRPM2 in ROS-Coupled Diseases

TRPM2 knockdown attenuates myocardial apoptosis and promotes autophagy in HFD/STZ-induced diabetic mice via regulating the MEK/ERK and mTORC1 signaling pathway

Contact Info

Product

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Ca²⁺ signalling in fibroblasts and the therapeutic potential of K_Ca3.1 channel blockers in fibrotic diseases

Ca²⁺ signalling in fibroblasts and the therapeutic potential of K_Ca3.1 channel blockers in fibrotic diseases