CD73‐derived adenosine and tenascin‐C control cytokine production by epicardium‐derived cells formed after myocardial infarction

Hesse, Julia; Leberling, Stella; Boden, E.; Friebe, Daniela; Schmidt, Tatjana; Ding, Zhaoping; Dieterich, Peter; Deußen, Andreas; Roderigo, Claudia; Rose, Christine R.; Floß, Doreen M.; Scheller, Jürgen; Schrader, Jürgen

doi:10.1096/fj.201601307r

Cited by 30 publications

(40 citation statements)

References 60 publications

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“…These cells can release IL‐1β and IL‐6 upon stimulation with LPS and ATP or BzATP. This effect is abolished after treatment with the P2X7 antagonist A740003 . The P2X7 expression on the heart was confirmed in different studies.…”

Section: P2x7 In the Heartmentioning

confidence: 53%

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P2X7 receptor in cardiovascular disease: The heart side

Martinez

2019

Clin Exp Pharma Physio

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Summary The P2X7 receptor is a ligand‐gated purinergic receptor activated by extracellular ATP. The receptor is highly expressed in immune cells and in the brain, and, upon activation, the P2X7 receptor allows a cation flux, leading to the distinct activation of intracellular signalling pathways as the secretion of pro‐inflammatory cytokines, and modulation of cell survival. Through these molecular mechanisms, P2X7 is known to play important roles in physiology and pathophysiology of a wide spectrum of diseases, including cancer, inflammatory diseases, neurological, respiratory and more recently cardiovascular diseases. Recent studies demonstrated that the P2X7 could modulate the assembly of the NLRP3 inflammasome, leading to the secretion of pro‐inflammatory factors and worsen the cardiac disease phenotypes. This review discusses the critical molecular function of P2X7 in the modulation of the onset, progression and resolution of cardiovascular diseases and analyses the putative future use of P2X7‐based therapies that modulate the IL‐1β secretion arm and direct P2X7 antagonists.

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Section: P2x7 In the Heartmentioning

confidence: 53%

“…133 This effect is abolished after treatment with the P2X7 antagonist A740003. 134 The P2X7 expression on the heart was confirmed in different studies. In the sinoatrial node and atria of the adult heart, the presence of the P2X7 receptor has already been detected through immunohistochemistry, qPCR and in situ hybridization.…”

Section: P2 X 7 In the He Artmentioning

confidence: 78%

P2X7 receptor in cardiovascular disease: The heart side

Martinez

2019

Clin Exp Pharma Physio

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“…Inhibition of CD73 with anti-CD73 antibodies or APCP reduced tumor angiogenesis in mice [30]. The mechenism is probably related to CD73's interaction with adenosine receptor A2B [31]. This interaction will stimulates vascular smooth muscle cells, endothelial cells, immune cells and tumor cells to secrete VEGF.…”

Section: Discussionmentioning

confidence: 99%

CD73 positive adipose derived mesenchymal stem cells enhance cardiac repair with experimental myocardial infarction by promoting angiogenesis

Li¹,

Hou

et al. 2020

Preprint

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Background: Cardiovascular disease is the leading cause of death in developed and developing countries. The lack of effective regenerative therapies in the treatment of ischemia‐related diseases requires new therapies to improve clinical outcomes. Thus, MSCs have become a focus in stem cell treatment of myocardial injury. At present, most studies use mixed MSCs in vivo and in vitro. A promising therapeutic strategy for myocardial injury should be using the dominant subgroup with essential biological characteristics. The aim of this study was to utilize the dominant CD73 + subgroup of adipose derived mesenchymal stem cells (ADMSCs) for the therapy of myocardial infarction (MI). Methods: Adult mix gender SD rats, with a body weight of 230±18g, were randomly divided into sham operation group (SHAM), MI group (MI), mixed ADMSCs transplantation group (MI+ADMSCs), CD73 + ADMSCs transplantation group (MI+CD73 + ADMSCs) and CD73 - ADMSCs transplantation group (MI+CD73 - ADMSCs). CD73 + ADMSCs were isolated using flow cytometry and then cultured. Overexpression and inhibition of CD73 gene of ADMSCs using lentiviral vectors. Differential genes analysis of CD73 + ADMSCs vs. CD73 - ADMSCs were based on GO analysis. The effect of CD73 on the secretion of cytokines was measured by ELISA. Myocardial infarction model and cell transplantation model were replicated. Detection of cardiac function of rats by color doppler ultrasound after operation. The expression of VEGF and factor VIII and neovascularization were detected by immunohistochemistry and Western Blotting. Results: We demonstrated that, compared to mixed ADMSCs and CD73 - ADMSCs, CD73 + ADMSCs were more effective in the promotion function of cardiac recovery in a rat model of MI. CD73 + subset promoted vascular regeneration in myocardial injured regions. We also showed that expression of CD73 promoted secretion of VEGF, HIF-1α and HGF factors in ADMSCs. CD73 + ADMSCs displayed significantly different transcription profile compared to CD73 - ADMSCs, in particular, concerning VEGF pathways. Conclusions: Overall, CD73 + ADMSCs were the dominant subgroup and the presence of the surface marker CD73 can be used as a MSCs cell quality control for treatment of myocardial injury by angiogenesis.

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“…Notably, Tnc is rapidly induced in adult tissues in response to pathological stress . Although Tnc is necessary for physiological tissue repair, its misregulated expression has been associated with a variety of pathological conditions, which include rheumatoid arthritis, cancer, myocardial infarction, hepatitis, and hepatic IRI . Tnc is a pleiotropic molecule implicated in various cellular functions, with regulation of cell adhesion and migration being among the most characterized .…”

mentioning

confidence: 99%

“…(16) Although Tnc is necessary for physiological tissue repair, its misregulated expression has been associated with a variety of pathological conditions, which include rheumatoid arthritis, cancer, myocardial infarction, hepatitis, and hepatic IRI. (17)(18)(19)(20)(21)(22) Tnc is a pleiotropic molecule implicated in various cellular functions, with regulation of cell adhesion and migration being among the most characterized. (18) Growing evidence now points to Tnc as a key regulator of both innate and adaptive immunity.…”

mentioning

confidence: 99%

Overproduction of Tenascin‐C Driven by Lipid Accumulation in the Liver Aggravates Hepatic Ischemia/Reperfusion Injury in Steatotic Mice

et al. 2019

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The purpose of this study was to assess the significance of tenascin‐C (Tnc) expression in steatotic liver ischemia/reperfusion injury (IRI). The critical shortage in donor organs has led to the use of steatotic livers in transplantation regardless of their elevated susceptibility to hepatic IRI. Tnc is an endogenous danger signal extracellular matrix molecule involved in various aspects of immunity and tissue injury. In the current study, mice were fed with a steatosis‐inducing diet and developed approximately 50% hepatic steatosis, predominantly macrovesicular, before being subjected to hepatic IRI. We report here that lipid accumulation in hepatocytes inflated the production of Tnc in steatotic livers and in isolated hepatic stellate cells. Moreover, we show that the inability of Tnc–/– deficient steatotic mice to express Tnc significantly protected these mice from liver IRI. Compared with fatty controls, Tnc–/– steatotic mice showed significantly reduced serum transaminase levels and enhanced liver histological preservation at both 6 and 24 hours after hepatic IRI. The lack of Tnc expression resulted in impaired lymphocyte antigen 6 complex, locus (Ly6G) neutrophil and macrophage antigen‐1 (Mac‐1) leukocyte recruitment as well as in decreased expression of proinflammatory mediators (interleukin 1β, tumor necrosis factor α, and chemokine [C‐X‐C motif] ligand 2) after liver reperfusion. Myeloperoxidase (MPO) is the most abundant cytotoxic enzyme secreted by neutrophils and a key mediator of neutrophil‐induced oxidative tissue injuries. Using an in vitro model of steatosis, we also show that Tnc markedly potentiated the effect of steatotic hepatocytes on neutrophil‐derived MPO activity. In conclusion, our data support the view that inhibition of Tnc is a promising therapeutic approach to lessen inflammation in steatotic livers and to maximize their successful use in organ transplantation.

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CD73‐derived adenosine and tenascin‐C control cytokine production by epicardium‐derived cells formed after myocardial infarction

Cited by 30 publications

References 60 publications

P2X7 receptor in cardiovascular disease: The heart side

P2X7 receptor in cardiovascular disease: The heart side

CD73 positive adipose derived mesenchymal stem cells enhance cardiac repair with experimental myocardial infarction by promoting angiogenesis

Overproduction of Tenascin‐C Driven by Lipid Accumulation in the Liver Aggravates Hepatic Ischemia/Reperfusion Injury in Steatotic Mice

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