Inhibition of transient receptor potential melastain 7 channel increases HSCs apoptosis induced by TRAIL

Lv, Hong; Li, Jun; Huang, Yan; Huang, Cheng

doi:10.1016/j.lfs.2012.02.012

Cited by 28 publications

(23 citation statements)

References 31 publications

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“…When arresting RBL-2H3 cells at various stages of the cell cycle, endogenous TRPM7-like currents are significantly upregulated at the G0/G1 transition (Tani et al 2007), further emphasizing the critical role of this channel at the transition stage from quiescence to proliferation. Differentiated mast cells, on the other hand, undergo apoptosis upon genetic suppression of TRPM7 (Ng et al 2012), and similar observations are made in hepatic stellate cells, possibly involving the TNF-related apoptosis-inducing ligand (TRAIL) mechanism (Liu et al 2012). Interestingly, proliferating rat embryonic hepatocytes and rat hepatoma show higher TRPM7 expression levels than adult nondividing rat hepatocytes, indicating that downregulation of endogenous TRPM7 is linked to the differentiation process (Lam et al 2012).…”

Section: Physiological Functions In Native Cells Organs and Organmentioning

confidence: 81%

Trpm7

Fleig

Chubanov

2014

Handbook of Experimental Pharmacology

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The channel kinases TRPM6 and TRPM7 are fusion proteins with an ion transport domain and an enzymatically active kinase domain. TRPM7 has been found in every mammalian tissue investigated to date. The two-in-one protein structure, the ubiquitous expression profile, and the protein’s unique biophysical characteristics that enable divalent ion transport involve TRPM7 in a plethora of (patho)physiological processes. With its prominent role in cellular and systemic magnesium homeostasis, TRPM7 emerges as a key player in embryonic development, global ischemia, cardiovascular disease, and cancer.

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Section: Physiological Functions In Native Cells Organs and Organmentioning

confidence: 81%

Trpm7

Fleig

Chubanov

2014

Handbook of Experimental Pharmacology

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“…It is intriguing that TRPM7 channel performs different functions in different cells. TRPM7 promotes the proliferation, migration or differentiation in several types of cells such as macrophage [ 41 ], hepatic stellate cells [ 42 ], human prostate cells [ 43 ], human lung fibroblast [ 44 ], and pre-adipocytes [ 45 ]. In contrast, TRPM7 channel plays a negative function in human umbilical endothelial cells (HUVECs) including inhibition of proliferation and migration and enhancement of hyperglycemia-induced injury [ 28 , 46 , 47 ].…”

Section: Discussionmentioning

confidence: 99%

Silencing TRPM7 in Mouse Cortical Astrocytes Impairs Cell Proliferation and Migration via ERK and JNK Signaling Pathways

et al. 2015

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Transient receptor potential melastatin 7 (TRPM7), a non-selective cation channel, is highly expressed expressed in the brain and plays a critical role in ischemic neuronal death. Astrocyte, the most abundant cell type in central nervous system (CNS), exerts many essential functions in the physiological and pathological conditions. Here we investigated the expression and functions of the TRPM7 channel in mouse cortical astrocytes. Using reverse transcription (RT)-PCR, immunostaining, western blot and patch clamp recording, we showed that functional TRPM7 channel is expressed in cultured mouse cortical astrocytes. Knocking down TRPM7 with specific siRNA impairs the proliferation and migration of astrocytes by 40.2% ± 3.9% and 40.1% ± 11.5%, respectively. Consistently, inhibition of TRPM7 with 2-aminoethoxydiphenyl borate (2-APB) also decreases astrocyte proliferation and migration by 46.1% ± 2.5% and 64.2% ± 2.4%. MAPKs and Akt signaling pathways have been shown to be implicated in TRPM7-mediated responses including cell proliferation and migration. Our data show that suppression of TRPM7 in astrocytes reduces the phosphorylation of extracellular signal-regulated kinases (ERK) and c-Jun N-terminal kinases (JNK), but not p38 mitogen-activated protein kinase and Akt. In addition, TRPM7, as a cation channel, has been involved in the Ca2+ and Mg2+ homeostasis in several types of cells. In our study, we found that silencing TRPM7 decreases the intracellular basal Mg2+ concentration without affecting Ca2+ concentration in astrocytes. However, an addition of Mg2+ to the growth medium could not rescue the impaired proliferation of astrocytes. Together, our data suggest that TRPM7 channel may play a critical role in the proliferation and migration of astrocytes via the ERK and JNK pathways.

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“…However, the molecular mechanisms responsible for the proliferation and activation of HSC are still unclear. In the case of HSC, this proliferation and activation responses can be prevented by treatment with chemical inhibitors of ion channels [4], [5]. But so far, the detailed mechanisms, by which ion channels regulate liver fibrosis, are complex and have not been fully elucidated.…”

Section: Introductionmentioning

confidence: 99%

TRPV4 Channel Inhibits TGF-β1-Induced Proliferation of Hepatic Stellate Cells

Song

Zhan

et al. 2014

PLoS ONE

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TRPV4, one of the TRP channels, is implicated in diverse physiological and pathological processes including cell proliferation. However, the role of TRPV4 in liver fibrosis is largely unknown. Here, we characterized the role of TRPV4 in regulating HSC-T6 cell proliferation. TRPV4 mRNA and protein were measured by RT-PCR and Western blot in patients and rat model of liver fibrosis in vivo and TGF-β1-activated HSC-T6 cells in vitro. Both mRNA and protein of TRPV4 were dramatically increased in liver fibrotic tissues of both patients and CCl4-treated rats. Stimulation of HSC-T6 cells with TGF-β1 resulted in increase of TRPV4 mRNA and protein. However, TGF-β1-induced HSC-T6 cell proliferation was inhibited by Ruthenium Red (Ru) or synthetic siRNA targeting TRPV4, and this was accompanied by downregulation of myofibroblast markers including α-SMA and Col1α1. Moreover, our study revealed that miR-203 was downregulated in liver fibrotic tissues and TGF-β1-treated HSC-T6 cell. Bioinformatics analyses predict that TRPV4 is the potential target of miR-203. In addition, overexpression of miR-203 in TGF-β1-induced HSC significantly reduced TRPV4 expression, indicating TRPV4, which was regulated by miR-203, may function as a novel regulator to modulate TGF-β1-induced HSC-T6 proliferation.

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Inhibition of transient receptor potential melastain 7 channel increases HSCs apoptosis induced by TRAIL

Cited by 28 publications

References 31 publications

Trpm7

Trpm7

Silencing TRPM7 in Mouse Cortical Astrocytes Impairs Cell Proliferation and Migration via ERK and JNK Signaling Pathways

TRPV4 Channel Inhibits TGF-β1-Induced Proliferation of Hepatic Stellate Cells

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