Role of adenosine A2B receptor signaling in contribution of cardiac mesenchymal stem-like cells to myocardial scar formation.
Role of adenosine A2B receptor signaling in contribution of cardiac mesenchymal stem-like cells to myocardial scar formation.
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腺苷 A2B 受体信号传导在心脏间充质干细胞样细胞对心肌疤痕形成的贡献中的作用。
DOI：
10.1007/s11302-014-9410-y
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发表时间：
2014
影响因子：
3.5
通讯作者：
Feoktistov,Igor
中科院分区：
文献类型：
--
作者：
Ryzhov,Sergey;Sung,BongHwan;Zhang,Qinkun;Weaver,Alissa;Gumina,RichardJ;Biaggioni,Italo;Feoktistov,Igor
腺苷水平在缺血心脏中增加，并有助于调节病理环境。我们先前表明，小鼠心脏Sca 1 + CD 31 −间充质基质细胞上的A2 B腺苷受体上调旁分泌因子的分泌，这可能有助于将这些细胞移植到梗死心脏时观察到的心脏恢复改善。在这项研究中，我们测试了A2 B受体信号传导调节心肌损伤后Sca 1 + CD 31 −细胞转变为肌成纤维细胞表型的假设，该表型促进心肌修复和重塑。在体外，TGFβ1诱导成肌纤维细胞标志物α-平滑肌肌动蛋白（αSMA）的表达，并增加Sca 1 + CD 31 −细胞中I型胶原的生成。刺激A2 B受体减弱TGFβ1诱导的I型胶原分泌，但对αSMA表达无影响。在体内，心肌梗死导致第5天α SMA阳性心脏基质细胞数量迅速增加，随后逐渐下降。A2 B受体的基因缺失对表达α SMA的基质细胞的初始积累没有影响，但加速了它们随后的下降;与A2 B基因敲除的心脏相比，野生型心脏中α SMA阳性细胞（包括Sca 1 + CD 31 −细胞）的数量仍然显著较高。因此，我们的研究揭示了心肌Sca 1 + CD 31 −细胞对梗死后α SMA表达细胞的积累有重要贡献，并通过延迟这些细胞的失活，暗示A2 B受体信号传导在心肌修复和重塑的调节中。这种现象可能有助于将这些细胞移植到受损心脏的有益效果。
Adenosine levels increase in ischemic hearts and contribute to the modulation of that pathological environment. We previously showed that A2Badenosine receptors on mouse cardiac Sca1+CD31−mesenchymal stromal cells upregulate secretion of paracrine factors that may contribute to the improvement in cardiac recovery seen when these cells are transplanted in infarcted hearts. In this study, we tested the hypothesis that A2Breceptor signaling regulates the transition of Sca1+CD31−cells, which occurs after myocardial injury, into a myofibroblast phenotype that promotes myocardial repair and remodeling. In vitro, TGFβ1 induced the expression of the myofibroblast marker α-smooth muscle actin (αSMA) and increased collagen I generation in Sca1+CD31−cells. Stimulation of A2Breceptors attenuated TGFβ1-induced collagen I secretion but had no effect on αSMA expression. In vivo, myocardial infarction resulted in a rapid increase in the numbers of αSMA-positive cardiac stromal cells by day 5 followed by a gradual decline. Genetic deletion of A2Breceptors had no effect on the initial accumulation of αSMA-expressing stromal cells but hastened their subsequent decline; the numbers of αSMA-positive cells including Sca1+CD31−cells remained significantly higher in wild type compared with A2Bknockout hearts. Thus, our study revealed a significant contribution of cardiac Sca1+CD31−cells to the accumulation of αSMA-expressing cells after infarction and implicated A2Breceptor signaling in regulation of myocardial repair and remodeling by delaying deactivation of these cells. It is plausible that this phenomenon may contribute to the beneficial effects of transplantation of these cells to the injured heart.
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影响因子：
11.2
作者：
Green,MD;Tephly,TR
通讯作者：
Tephly,TR
兔肝雌酮和对硝基苯酚 UDP-葡萄糖醛酸转移酶特性的纯化。
影响因子：
3.9
作者：
Tukey,RH;Tephly,TR
通讯作者：
Tephly,TR
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DOI：
--
发表时间：
1984
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Kirkpatrick,RB;Falany,CN;Tephly,TR
通讯作者：
Tephly,TR
肝微粒体 UDP-葡萄糖醛酸基转移酶活性的异质性：人类和哺乳动物物种活性之间的比较。
影响因子：
5.1
作者：
J. Boutin;B. Antoine;A. Batt;G. Siest
通讯作者：
G. Siest
大鼠和人肝微粒体中致癌芳香胺的 N-葡萄糖苷酸形成。
影响因子：
5.8
作者：
W. Lilienblum;K. Bock
通讯作者：
K. Bock