Hesse 2021 FASEB J: Difference between revisions
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|area=Respiration, nDNA;cell genetics | |area=Respiration, nDNA;cell genetics | ||
|injuries=Hypoxia | |||
|organism=Rat | |organism=Rat | ||
|tissues=Heart, Fibroblast | |tissues=Heart, Fibroblast |
Latest revision as of 09:01, 13 August 2021
Hesse J, Groterath W, Owenier C, Steinhausen J, Ding Z, Steckel B, Czekelius C, Alter C, Marzoq A, Schrader J (2021) Normoxic induction of HIF-1ฮฑ by adenosine-A2B R signaling in epicardial stromal cells formed after myocardial infarction. FASEB J 35:21517. |
Hesse Julia, Groterath Wiebke, Owenier Christoph, Steinhausen Julia, Ding Zhaoping, Steckel Bodo, Czekelius Constantin, Alter Christina, Marzoq Aseel, Schrader Juergen (2021) FASEB J
Abstract: Myocardial infarction (MI) activates the epicardium to form epicardial stromal cells (EpiSC) that reside in the epicardial hypoxic microenvironment. Paracrine factors secreted by EpiSC were shown to modulate the injury response of the post-MI heart and improve cardiac function. We have previously reported that the expression of the angiogenic cytokines vascular endothelial growth factor A (VEGFA) and IL-6 is strongly upregulated in EpiSC by adenosine acting via the A2B receptor (A2B R). Since tissue hypoxia is well known to be a potent stimulus for the generation of extracellular adenosine, the present study explored the crosstalk of A2B R activation and hypoxia-hypoxia-inducible factor 1 alpha (HIF-1ฮฑ) signaling in cultured EpiSC, isolated from rat hearts 5 days after MI. We found substantial nuclear accumulation of HIF-1ฮฑ after A2B R activation even in the absence of hypoxia. This normoxic HIF-1ฮฑ induction was PKC-dependent and involved upregulation of HIF-1ฮฑ mRNA expression. While the influence of hypoxia on adenosine generation and A2B R signaling was only minor, hypoxia and A2B R activation cumulatively increased VEGFA expression. Normoxic A2B R activation triggered an HIF-1ฮฑ-associated cell-protective metabolic switch and reduced oxygen consumption. HIF-1ฮฑ targets and negative regulators PHD2 and PHD3 were only weakly induced by A2B R signaling, which may result in a sustained HIF-1ฮฑ activity. The A2B R-mediated normoxic HIF-1ฮฑ induction was also observed in cardiac fibroblasts from healthy mouse hearts, suggesting that this mechanism is also functional in other A2B R-expressing cell types. Altogether, we identified A2B R-mediated HIF-1ฮฑ induction as novel aspect in the HIF-1ฮฑ-adenosine crosstalk, which modulates EpiSC activity and can amplify HIF-1ฮฑ-mediated cardioprotection. โข Keywords: A2B receptor, HIF-1ฮฑ, Cardioprotection, Hypoxia, Myocardial infarction โข Bioblast editor: Reiswig R
Labels: MiParea: Respiration, nDNA;cell genetics
Stress:Hypoxia Organism: Rat Tissue;cell: Heart, Fibroblast Preparation: Intact cells
Coupling state: ROUTINE
HRR: Oxygraph-2k
2021-08