Mild Electrical Stimulation at 0.1-ms Pulse Width Induces p53 Protein Phosphorylation and G2 Arrest in Human Epithelial Cells

Fukuda, Ryosuke; Suico, Mary Ann; Koyama, Kosuke; Omachi, Kohei; Kai, Yukari; Matsuyama, Shingo; Mitsutake, Kazunori; Taura, Manabu; Morino-Koga, Saori; Shuto, Tsuyoshi; Kai, Hirofumi

doi:10.1074/jbc.m112.442442

Cited by 18 publications

(20 citation statements)

References 63 publications

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“…Endogenous electrical field (EF) is known to play an important role in development and is thus an attractive cue to induce stem cell differentiation (Mooney et al ., ; Thrivikraman et al ., ). Electrical stimulation (ES) was shown to increase DNA synthesis (Bourguignon and Bourguignon, ), activate p53 (Fukuda et al ., ), increase TGF β receptor expression (Falanga et al ., ) and upregulate fibroblast growth factor secretion (Rouabhia et al ., ). Cells also responded to exogenous ES via intracellular signalling pathways, such as phosphatidylinositol‐3‐OH kinase (PI3K)–Akt, MAPK–ERKs, integrin and Rho (Fukata et al ., ; Li et al ., ).…”

Section: Introductionmentioning

confidence: 99%

Pulsed electrical stimulation modulates fibroblasts' behaviour through the Smad signalling pathway

Wang

Rouabhia

Lavertu

et al. 2015

J Tissue Eng Regen Med

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The aim of this study was to investigate the healing characteristics and the underlying signalling pathway of human dermal fibroblasts under the influence of pulsed electrical stimulation (PES). Primary human dermal fibroblasts were seeded on polypyrrole-coated polyester fabrics and subjected to four different PES protocols. The parameters of the rectangular pulse included potential intensity (50 and 100 mV/mm) and stimulation time (pulse width 300 s within a period of 600 s, and pulse width 10 s within a period of 1200 s). Our study revealed that PES moderately improved the ability of the cells to migrate in association with a statistically significant (p < 0.05) increase of FGF2 secretion by the PES-exposed fibroblasts. These exposed fibroblasts were able to contract collagen gel matrix up to 48 h and this collagen gel contraction paralleled an increase in α-SMA mRNA expression and protein production from the PES-exposed fibroblasts. Interestingly, the effect of PES on the human fibroblasts involved the Smad signalling pathway, as we observed higher levels of phosphorylated Smad2 and Smad3 in the stimulated groups compared to the control groups. Overall, this study demonstrated that PES modulates fibroblast activities through the Smad signalling pathway, thus providing new mechanistic insights related to the use of PES to promote wound healing in humans. Copyright © 2015 John Wiley & Sons, Ltd.

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Section: Introductionmentioning

confidence: 99%

Pulsed electrical stimulation modulates fibroblasts' behaviour through the Smad signalling pathway

Wang

Rouabhia

Lavertu

et al. 2015

J Tissue Eng Regen Med

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“…The therapeutic effects of combination treatment (MES+HS) are higher than those of MES alone or HS alone. In addition, we showed that MES+HS exerts biological effects via activation of intracellular signaling pathways such as p53 and LKB1‐AMPK axis . In clinical studies for subjects with type 2 diabetes mellitus and metabolic syndrome, MES+HS treatment significantly ameliorated the insulin resistance and inflammatory parameters without any adverse effects .…”

Section: Introductionmentioning

confidence: 86%

Mild electrical stimulation with heat shock reduces inflammatory symptoms in the imiquimod‐induced psoriasis mouse model

Tsurekawa

Morita

Suico

et al. 2018

Experimental Dermatology

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Psoriasis is a chronic skin disease caused by immune disorder. The chronic skin inflammation involves inflammatory molecules that are released from T lymphocytes and keratinocytes. Therefore, developing an anti-inflammatory therapy that is suitable for long-term treatment is needed. Electrical stimulation induces biological responses by modulating intracellular signaling pathways. Our previous studies showed that the optimized combination treatment of mild electrical stimulation (MES, 0.1-millisecond; ms, 55-pulses per second; pps) and heat shock (HS, 42°C) modulates inflammatory symptoms of metabolic disorders and chronic kidney disease in mice models and clinical trials. Here, we investigated the effect of MES+HS treatment on imiquimod-induced psoriasis mouse model. Topical application of imiquimod cream (15 mg) to mice ear induced keratinocyte hyperproliferation and psoriasis-like inflammation. In MES+HS-treated mice, imiquimod-induced skin hyperplasia was significantly decreased. MES+HS treatment reduced the protein expression of IL-17A and the infiltration of CD3-positive cells in lesioned skin. In addition, MES+HS-treated mice had decreased mRNA expression level of antimicrobial molecules (S100A8 and Reg3γ) which aggravate psoriasis. In IL-17A-stimulated HaCaT cells, MES+HS treatment significantly lowered the mRNA expression of aggravation markers (S100A8, S100A9 and β-defensin2). Taken together, our study suggested that MES+HS treatment improves the pathology of psoriasis via decreasing the expression of inflammatory molecules.

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“…Considering that MES is a form of physiological stress, it is conceivable that the latter can activate the tumor suppressor p53, which is a key modulator of the cell cycle and apoptosis in response to cell stresses. Indeed, when cells were treated with an imperceptible voltage (1 V/cm) p53 was transiently phosphorylated at Ser‐15 by p38 MAPK (Fukuda et al, ). Therefore, it can be concluded that electrical stimulation activates p53 and may induce p53‐dependent differentiation of MSCs (Tonelli et al, ).…”

Section: Ca2+‐depended Signaling Pathway Regulates Self‐renewal and Pmentioning

confidence: 99%

Ca²⁺‐depended signaling pathways regulate self‐renewal and pluripotency of stem cells

Ермаков

Daks

Fedorova

et al. 2018

Cell Biology International

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Ca -mediated signaling is widely spread in nature and plays critical role in the individual development of various organisms ranging from microorganisms to mammals. In vertebrates, Ca is involved in important developmental events: fertilization, body plan establishment, and organogenesis. The two later events are defined by embryonic stem cells (ESCs). ESCs are capable of self-renewal and are pluripotent by nature, that is, can give rise to all types of cells that make up the body. Given the paramount importance of Ca signalization in the development, it is therefore not surprising this process also plays role in the biology of stem cells. In this review, we scrutinize the published experimental data on the role of Ca ions in embryonic stem cells self-renewal and pluripotency. In line with this, we also discuss possible mechanisms of p53 inhibition as a major hindrance to self-renewal of ESCs. Finally, we argue about the role of G-protein-coupled receptors (GPCRs), the largest family of heteromeric transmembrane receptors, and GPCR-mediated signalization in stem cells, and propose the role for the GPCR-G-protein-PLC-Ca -downstream signaling pathway in the regulation of pluripotency of both mouse and human ESCs.

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Mild Electrical Stimulation at 0.1-ms Pulse Width Induces p53 Protein Phosphorylation and G2 Arrest in Human Epithelial Cells

Cited by 18 publications

References 63 publications

Pulsed electrical stimulation modulates fibroblasts' behaviour through the Smad signalling pathway

Pulsed electrical stimulation modulates fibroblasts' behaviour through the Smad signalling pathway

Mild electrical stimulation with heat shock reduces inflammatory symptoms in the imiquimod‐induced psoriasis mouse model

Ca²⁺‐depended signaling pathways regulate self‐renewal and pluripotency of stem cells

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Mild Electrical Stimulation at 0.1-ms Pulse Width Induces p53 Protein Phosphorylation and G2 Arrest in Human Epithelial Cells

Cited by 18 publications

References 63 publications

Pulsed electrical stimulation modulates fibroblasts' behaviour through the Smad signalling pathway

Pulsed electrical stimulation modulates fibroblasts' behaviour through the Smad signalling pathway

Mild electrical stimulation with heat shock reduces inflammatory symptoms in the imiquimod‐induced psoriasis mouse model

Ca2+‐depended signaling pathways regulate self‐renewal and pluripotency of stem cells

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Ca²⁺‐depended signaling pathways regulate self‐renewal and pluripotency of stem cells