Role of A<sub>2B</sub>Adenosine Receptors in Regulation of Paracrine Functions of Stem Cell Antigen 1-Positive Cardiac Stromal Cells

Ryzhov, Sergey; Goldstein, Anna E.; Novitskiy, Sergey V.; Blackburn, Michael R.; Biaggioni, Italo; Feoktistov, Igor

doi:10.1124/jpet.111.190835

Cited by 28 publications

(38 citation statements)

References 50 publications

(85 reference statements)

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“…Adenosine has long been known to stimulate vascular endothelial growth factor (VEGF) production and angiogenesis (for reviews, see Adair, 2005;Feoktistov et al, 2009). In particular, we demonstrated that stimulation of A 2B adenosine receptors upregulated VEGF secretion in various cell types, including cardiac mesenchymal stem-like cells (Ryzhov et al, 2012), retinal and skin endothelial cells (Grant et al, 1999(Grant et al, , 2001Feoktistov et al, 2002), certain types of cancer cells (Zeng et al, 2003;Ryzhov et al, 2008a), tumorinfiltrating hematopoietic cells (Ryzhov et al, 2008a), and mast cells (Feoktistov and Biaggioni, 1995;Feoktistov et al, 2003;Ryzhov et al, 2008b). This work was supported by the National Institutes of Health National Heart, Lung, and Blood Institute [Grant R01 HL095787] (to I.F.…”

Section: Introductionmentioning

confidence: 77%

“…2 stromal cells (mCSC) were isolated as previously described elsewhere (Ryzhov et al, 2012). Cells were propagated on 0.1% gelatin-coated tissue culture dishes in DMEM-high glucose supplemented with 10% FBS, 2 mM glutamine, 10 ng/ml basic fibroblast growth factor, and 10 ng/ml interferon-g at 33°C.…”

Section: Cd31mentioning

confidence: 99%

“…One microgram of total DNase-treated RNA was used to generate cDNA with MMLV RT (Promega, Madison, WI) and random hexamers (Applied Biosystems, Foster City, CA). Reversetranscription polymerase chain reaction was performed using the ABI PRISM 7900HT Sequence Detection System (Applied Biosystems), as described previously elsewhere (Ryzhov et al, 2012). Primer pairs for human and murine adenosine receptors (A 1 , A 2A , A 2B , A 3 ) were obtained from Applied Biosystems (human AdoRs: Hs00181231, Hs00169123, Hs00386497, and Hs00181232; and murine AdoRs: Mm01308023, Mm00802075, Mm00839292, and Mm00802076).…”

Section: Cd31mentioning

confidence: 99%

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Role of JunB in Adenosine A_2BReceptor–Mediated Vascular Endothelial Growth Factor Production

et al. 2013

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Interstitial adenosine stimulates neovascularization in part through A 2B adenosine receptor-dependent upregulation of vascular endothelial growth factor (VEGF). In the current study, we tested the hypothesis that A 2B receptors upregulate JunB, which can contribute to stimulation of VEGF production. Using the human microvascular endothelial cell line, human mast cell line, mouse cardiac Sca1-positive stromal cells, and mouse Lewis lung carcinoma (LLC) cells, we found that adenosine receptordependent upregulation of VEGF production was associated with an increase in VEGF transcription, activator protein-1 (AP-1) activity, and JunB accumulation in all cells investigated. Furthermore, the expression of JunB, but not the expression of other genes encoding transcription factors from the Jun family, was specifically upregulated. In LLC cells expressing A 2A and A 2B receptor transcripts, only the nonselective adenosine agonist NECA (59-N-ethylcarboxamidoadenosine), but not the selective A 2A receptor agonist CGS21680 [2-p-(2-carboxyethyl) phenylethylamino-59-N-ethylcarboxamidoadenosine], significantly increased JunB reporter activity and JunB nuclear accumulation, which were inhibited by the A 2B receptor antagonist PSB603 [(8-[4-[4-((4-chlorophenzyl)piperazide-1-sulfonyl)phenyl]]-1-propylxanthine]. Using activators and inhibitors of intracellular signaling, we demonstrated that A 2B receptor-dependent accumulation of JunB protein and VEGF secretion share common intracellular pathways. NECA enhanced JunB binding to the murine VEGF promoter, whereas mutation of the high-affinity AP-1 site (21093 to 21086) resulted in a loss of NECA-dependent VEGF reporter activity. Finally, NECA-dependent VEGF secretion and reporter activity were inhibited by the expression of a dominant negative JunB or by JunB knockdown. Thus, our data suggest an important role of the A 2B receptor-dependent upregulation of JunB in VEGF production and possibly other AP-1-regulated events.

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Section: Introductionmentioning

confidence: 77%

Section: Cd31mentioning

confidence: 99%

Section: Cd31mentioning

confidence: 99%

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Role of JunB in Adenosine A_2BReceptor–Mediated Vascular Endothelial Growth Factor Production

et al. 2013

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“…First, we established the P1 purinergic receptor profile of CPCs, which correlated well with that of MSCs as they are reported to express A1 [7], A2A [21], and A2B [46], but no A3 receptors. In particular, A1 and A2B receptor-mediated signalling is known to be required for osteogenic differentiation of MSCs [7,48].…”

Section: Purinergic Signalling In Cpcs and Autocrine/paracrine Regulamentioning

confidence: 85%

Purinergic signalling is required for calcium oscillations in migratory chondrogenic progenitor cells

Matta

Fodor

Miosge

et al. 2014

Pflugers Arch - Eur J Physiol

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Osteoarthritis (OA) is the most common form of chronic musculoskeletal disorders. A migratory stem cell population termed chondrogenic progenitor cells (CPC) with in vitro chondrogenic potential was previously isolated from OA cartilage. Since intracellular Ca 2+ signalling is an important regulator of chondrogenesis, we aimed to provide a detailed understanding of the Ca 2+ homeostasis of CPCs. In this work, CPCs immortalised by lentiviral administration of the human telomerase reverse transcriptase (hTERT) and grown in monolayer cultures were studied. Expressions of all three IP3Rs were confirmed, but no RyR subtypes were detected. Ca 2+ oscillations observed in CPCs were predominantly dependent on Ca 2+ release and store replenishment via store-operated Ca 2+ entry; CPCs express both STIM1 and Orai1 proteins. Expressions of adenosine receptor mRNAs were verified, and adenosine elicited Ca 2+ transients. Various P2 receptor subtypes were identified; P2Y1 can bind ADP; P2Y4 is targeted by UTP; and ATP may evoke Ca 2+ transients via detected P2X subtypes, as well as P2Y1 and P2Y2. Enzymatic breakdown of extracellular nucleotides by apyrase completely abrogated Ca 2+ oscillations, suggesting that an autocrine/paracrine purinergic mechanism may drive Ca 2+ oscillations in these cells.As CPCs possess a broad spectrum of functional molecular elements of Ca 2+ signalling, Ca 2+ -dependent regulatory mechanisms can be supposed to influence their differentiation potential.

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“…neg cardiac cells represented a subpopulation of cardiac progenitors in adult hearts, characterized by a capability to differentiate toward endothelial cells and cardiac myocytes (6,32,46,51,53). These cells play a protective role in MI (47,53).…”

Section: Cd31mentioning

confidence: 99%

Effects of vitamin A deficiency in the postnatal mouse heart: role of hepatic retinoid stores

Asson-Batres

Ryzhov

Tikhomirov

et al. 2016

American Journal of Physiology-Heart and Circulatory Physiology

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To determine whether hepatic depletion of vitamin A (VA) stores has an effect on the postnatal heart, studies were carried out with mice lacking liver retinyl ester stores fed either a VA-sufficient (LRVAS) or VA-deficient (LRVAD) diet (to deplete circulating retinol and extrahepatic stores of retinyl esters). There were no observable differences in the weights or gross morphology of hearts from LRVAS or LRVAD mice relative to sex-matched, agematched, and genetically matched wild-type (WT) controls fed the VAS diet (WTVAS), but changes in the transcription of functionally relevant genes were consistent with a state of VAD in LRVAS and LRVAD ventricles. In silico analysis revealed that 58/67 differentially expressed transcripts identified in a microarray screen are products of genes that have DNA retinoic acid response elements. Flow cytometric analysis revealed a significant and cell-specific increase in the number of proliferating Sca-1 cardiac progenitor cells in LRVAS animals relative to WTVAS controls. Before myocardial infarction, LRVAS and WTVAS mice had similar cardiac systolic function and structure, as measured by echocardiography, but, unexpectedly, repeat echocardiography demonstrated that LRVAS mice had less adverse remodeling by 1 wk after myocardial infarction. Overall, the results demonstrate that the adult heart is responsive to retinoids, and, most notably, reducing hepatic VA stores (while maintaining circulating levels of VA) impacts ventricular gene expression profiles, progenitor cell numbers, and response to injury.heart; lecithin retinyl acyl transferase; postnatal; retinoic acid; vitamin A NEW & NOTEWORTHYWe demonstrate heart-wide expression of retinoic acid receptor-␥, a retinoic acid-activated nuclear receptor, and report that ventricles from adult mice with depleted hepatic vitamin A stores have altered gene expression, a significant increase in proliferating progenitor cells, and improved response to acute myocardial injury.

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Role of A_2BAdenosine Receptors in Regulation of Paracrine Functions of Stem Cell Antigen 1-Positive Cardiac Stromal Cells

Cited by 28 publications

References 50 publications

Role of JunB in Adenosine A_2BReceptor–Mediated Vascular Endothelial Growth Factor Production

Role of JunB in Adenosine A_2BReceptor–Mediated Vascular Endothelial Growth Factor Production

Purinergic signalling is required for calcium oscillations in migratory chondrogenic progenitor cells

Effects of vitamin A deficiency in the postnatal mouse heart: role of hepatic retinoid stores

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Role of A2BAdenosine Receptors in Regulation of Paracrine Functions of Stem Cell Antigen 1-Positive Cardiac Stromal Cells

Cited by 28 publications

References 50 publications

Role of JunB in Adenosine A2BReceptor–Mediated Vascular Endothelial Growth Factor Production

Role of JunB in Adenosine A2BReceptor–Mediated Vascular Endothelial Growth Factor Production

Purinergic signalling is required for calcium oscillations in migratory chondrogenic progenitor cells

Effects of vitamin A deficiency in the postnatal mouse heart: role of hepatic retinoid stores

Contact Info

Product

Resources

About

Role of A_2BAdenosine Receptors in Regulation of Paracrine Functions of Stem Cell Antigen 1-Positive Cardiac Stromal Cells

Role of JunB in Adenosine A_2BReceptor–Mediated Vascular Endothelial Growth Factor Production

Role of JunB in Adenosine A_2BReceptor–Mediated Vascular Endothelial Growth Factor Production