Role of the store-operated Ca𝟐+ channel in ATP-induced Ca𝟐+ signalling in mesenchymal stem cells and regulation of cell functions

Wang, Lu; Roger, Sébastien; Yang, Xuebin; Jiang, Linhua

doi:10.52586/5065

Cited by 8 publications

(4 citation statements)

References 104 publications

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“…It has also been established that cells express a wide range of purine-specific receptors and enzymes that are involved in this molecular machinery [ 93 , 94 , 95 , 96 , 97 ] ( Figure 1 ). Through P-type receptor activation, extracellular nucleotides trigger trophic effects and regulate many processes of MSCs, including proliferation, cell death, migration, and differentiation [ 78 , 93 , 98 , 99 ].…”

Section: Functional Attributes Of Mesenchymal Stem Cells Revisitedmentioning

confidence: 99%

Mesenchymal Stem Cells and Purinergic Signaling in Autism Spectrum Disorder: Bridging the Gap between Cell-Based Strategies and Neuro-Immune Modulation

Wikarska,

Roszak,

Roszek

2024

Biomedicines

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The prevalence of autism spectrum disorder (ASD) is still increasing, which means that this neurodevelopmental lifelong pathology requires special scientific attention and efforts focused on developing novel therapeutic approaches. It has become increasingly evident that neuroinflammation and dysregulation of neuro-immune cross-talk are specific hallmarks of ASD, offering the possibility to treat these disorders by factors modulating neuro-immunological interactions. Mesenchymal stem cell-based therapy has already been postulated as one of the therapeutic approaches for ASD; however, less is known about the molecular mechanisms of stem cell influence. One of the possibilities, although still underestimated, is the paracrine purinergic activity of MSCs, by which stem cells ameliorate inflammatory reactions. Modulation of adenosine signaling may help restore neurotransmitter balance, reduce neuroinflammation, and improve overall brain function in individuals with ASD. In our review article, we present a novel insight into purinergic signaling, including but not limited to the adenosinergic pathway and its role in neuroinflammation and neuro-immune cross-talk modulation. We anticipate that by achieving a greater understanding of the purinergic signaling contribution to ASD and related disorders, novel therapeutic strategies may be devised for patients with autism in the near future.

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Section: Functional Attributes Of Mesenchymal Stem Cells Revisitedmentioning

confidence: 99%

Mesenchymal Stem Cells and Purinergic Signaling in Autism Spectrum Disorder: Bridging the Gap between Cell-Based Strategies and Neuro-Immune Modulation

Wikarska,

Roszak,

Roszek

2024

Biomedicines

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“…A crucial role in the pathogenic mechanism of ACM can be played by the fibro-adipogenic differentiation of cardiac mesenchymal stromal cells (C-MSCs), which renders the cardiac tissue more likely to develop the arrhythmic events leading to the patient’s death [ 2 , 3 ]. Intriguingly, a recent investigation showed that the I c antiarrhythmic drug (AAD) flecainide inhibited fibro-adipose differentiation in human C-MSCs (C-hMSCs) expanded from ACM patients (ACM C-hMSCs) by blocking store-operated Ca 2+ entry (SOCE) [ 4 ], which represents the most important Ca 2+ entry pathway in non-excitable cells [ 5 , 6 , 7 ], including MSCs [ 8 , 9 , 10 ]. Herein, we first describe the genetic background and therapeutic options of ACM.…”

Section: Introductionmentioning

confidence: 99%

Store-Operated Ca2+ Entry as a Putative Target of Flecainide for the Treatment of Arrhythmogenic Cardiomyopathy

Moccia

Brunetti

Soda

et al. 2023

JCM

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Arrhythmogenic cardiomyopathy (ACM) is a genetic disorder that may lead patients to sudden cell death through the occurrence of ventricular arrhythmias. ACM is characterised by the progressive substitution of cardiomyocytes with fibrofatty scar tissue that predisposes the heart to life-threatening arrhythmic events. Cardiac mesenchymal stromal cells (C-MSCs) contribute to the ACM by differentiating into fibroblasts and adipocytes, thereby supporting aberrant remodelling of the cardiac structure. Flecainide is an Ic antiarrhythmic drug that can be administered in combination with β-adrenergic blockers to treat ACM due to its ability to target both Nav1.5 and type 2 ryanodine receptors (RyR2). However, a recent study showed that flecainide may also prevent fibro-adipogenic differentiation by inhibiting store-operated Ca2+ entry (SOCE) and thereby suppressing spontaneous Ca2+ oscillations in C-MSCs isolated from human ACM patients (ACM C-hMSCs). Herein, we briefly survey ACM pathogenesis and therapies and then recapitulate the main molecular mechanisms targeted by flecainide to mitigate arrhythmic events, including Nav1.5 and RyR2. Subsequently, we describe the role of spontaneous Ca2+ oscillations in determining MSC fate. Next, we discuss recent work showing that spontaneous Ca2+ oscillations in ACM C-hMSCs are accelerated to stimulate their fibro-adipogenic differentiation. Finally, we describe the evidence that flecainide suppresses spontaneous Ca2+ oscillations and fibro-adipogenic differentiation in ACM C-hMSCs by inhibiting constitutive SOCE.

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“…As a ubiquitous and important second messenger substance, Ca 2+ is widely involved in important pathophysiological processes in cells, and its small changes can affect the normal physiological function of cells. Ca 2+ influx is a key link in the signal transduction process of activation of hepatic stellate cells ( Li et al, 2020 ; Wang et al, 2021a ). Calmodulin (CaM) is widely expressed in various cells.…”

Section: Introductionmentioning

confidence: 99%

CaM/CaMKII mediates activation and proliferation of hepatic stellate cells regulated by ASIC1a

Liu

Hong

et al. 2022

Front. Pharmacol.

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The activation of hepatic stellate cells (HSCs) is closely related to hepatic fibrosis and plays a key role in its occurrence and development. In the damaged liver, inhibition of the activation, proliferation, and clearance of HSCs is an important therapeutic strategy. However, the mechanism underlying the activation of HSCs is not completely clear. Acid-sensitive ion channel 1a (ASIC1a) is a cation channel activated by extracellular acid, which is responsible for the transport of Ca2+ and Na+ and participates in the activation of HSCs and the occurrence and development of many inflammatory diseases, suggesting that ASIC1a plays an important role in liver fibrosis. A previous study by the project team found that when the membrane channel protein ASIC1a was opened, intracellular Ca2+ levels increased, the expression of CaM/CaMKII in HSCs was high, and HSC was activated and proliferated. Therefore, we established an SD rat model of hepatic fibrosis and induced HSC-T6 activation by stimulating ASIC1a with acid in vitro. In vivo, CCl4 was used to induce liver fibrosis in rats, and different doses of KN93 (0.5, 1, and 2 mg/kg/d) and colchicine (0.1 mg/kg/d) were administered. Eight weeks later, the activities of ALT and AST in serum were measured and hematoxylin-eosin and Masson staining in liver tissue, and immunohistochemistry analysis were performed in SD rats. The expressions of ASIC1a, α-SMA, Collagen-1, CaM, and CaMKII were detected. In vitro, we activated HSC-T6 cells by stimulating ASIC1a with acid. The results showed that inhibition of ASIC1a could improve acid-induced HSCs activation. In addition, CaM/CaMKII was expressed in HSC of rats with hepatic fibrosis regulated by ASIC1a. After blocking or silencing the expression of CaMKII, the fibrosis marker protein can be down-regulated. KN93 also reduced inflammation and improved the activation, proliferation and fibrosis of HSC. In summary, we concluded that CaM/CaMKII participates in ASIC1a regulation of the proliferation and activation of HSC and promotes the occurrence of liver fibrosis.

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Role of the store-operated Ca𝟐+ channel in ATP-induced Ca𝟐+ signalling in mesenchymal stem cells and regulation of cell functions

Cited by 8 publications

References 104 publications

Mesenchymal Stem Cells and Purinergic Signaling in Autism Spectrum Disorder: Bridging the Gap between Cell-Based Strategies and Neuro-Immune Modulation

Mesenchymal Stem Cells and Purinergic Signaling in Autism Spectrum Disorder: Bridging the Gap between Cell-Based Strategies and Neuro-Immune Modulation

Store-Operated Ca2+ Entry as a Putative Target of Flecainide for the Treatment of Arrhythmogenic Cardiomyopathy

CaM/CaMKII mediates activation and proliferation of hepatic stellate cells regulated by ASIC1a

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