title: CD73-derived adenosine and tenascin-C control cytokine production by epicardium-derived cells formed after myocardial infarction.
abstract: Epicardium-derived cells (EPDCs) play a fundamental role in embryonic cardiac development and are reactivated in the adult heart in response to myocardial infarction (MI). In this study, EPDCs from post-MI rat hearts highly expressed the ectoenzyme CD73 and secreted the profibrotic matricellular protein tenascin-C (TNC). CD73 on EPDCs extensively generated adenosine from both extracellular ATP and NAD. This in turn stimulated the release of additional nucleotides from a Brefeldin A-sensitive intracellular poolviaadenosine-A2BR signaling, forming a positive-feedback loop. A2BR activation, in addition, strongly promoted the release of major regulatory cytokines, such as IL-6, IL-11, and VEGF. TNC was found to stimulate EPDC migration and, together with ATP-P2X7R signaling, to activate inflammasomes in EPDCsviaTLR4. Our results demonstrate that EPDCs are an important source of various proinflammatory factors in the post-MI heart controlled by purinergic and TNC signaling.-Hesse, J., Leberling, S., Boden, E., Friebe, D., Schmidt, T., Ding, Z., Dieterich, P., Deussen, A., Roderigo, C., Rose, C. R., Floss, D. M., Scheller, J., Schrader, J. CD73-derived adenosine and tenascin-C control cytokine production by epicardium-derived cells formed after myocardial infarction.
authors.affiliation: Department of Molecular Cardiology, Heinrich Heine University Düsseldorf, Düsseldorf, Germany.
authors.forename: Julia
authors.initials: J
authors.lastname: Hesse
authors.affiliation: Department of Molecular Cardiology, Heinrich Heine University Düsseldorf, Düsseldorf, Germany.
authors.forename: Stella
authors.initials: S
authors.lastname: Leberling
authors.affiliation: Department of Molecular Cardiology, Heinrich Heine University Düsseldorf, Düsseldorf, Germany.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Boden
authors.affiliation: Department of Molecular Cardiology, Heinrich Heine University Düsseldorf, Düsseldorf, Germany.
authors.forename: Daniela
authors.initials: D
authors.lastname: Friebe
authors.affiliation: Department of Molecular Cardiology, Heinrich Heine University Düsseldorf, Düsseldorf, Germany.
authors.forename: Timo
authors.initials: T
authors.lastname: Schmidt
authors.affiliation: Department of Molecular Cardiology, Heinrich Heine University Düsseldorf, Düsseldorf, Germany.
authors.forename: Zhaoping
authors.initials: Z
authors.lastname: Ding
authors.affiliation: Institute of Physiology, Medical Faculty Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Dieterich
authors.affiliation: Institute of Physiology, Medical Faculty Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Deussen
authors.affiliation: Institute of Neurobiology, Heinrich Heine University Düsseldorf, Düsseldorf, Germany.
authors.forename: Claudia
authors.initials: C
authors.lastname: Roderigo
authors.affiliation: Institute of Neurobiology, Heinrich Heine University Düsseldorf, Düsseldorf, Germany.
authors.forename: Christine R
authors.initials: CR
authors.lastname: Rose
authors.affiliation: Institute of Biochemistry and Molecular Biology II, Heinrich Heine University Düsseldorf, Düsseldorf, Germany.
authors.forename: Doreen M
authors.initials: DM
authors.lastname: Floss
authors.affiliation: Institute of Biochemistry and Molecular Biology II, Heinrich Heine University Düsseldorf, Düsseldorf, Germany.
authors.forename: Jürgen
authors.initials: J
authors.lastname: Scheller
authors.affiliation: Department of Molecular Cardiology, Heinrich Heine University Düsseldorf, Düsseldorf, Germany; schrader@uni-duesseldorf.de.
authors.forename: Jürgen
authors.initials: J
authors.lastname: Schrader
mesh_terms: D015720:5'-Nucleotidase / Q000378:metabolism*; D000241:Adenosine / Q000378:metabolism*; D000818:Animals; D016207:Cytokines / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000502:physiology; D008297:Male; D009203:Myocardial Infarction / Q000378:metabolism / Q000473:pathology; D010496:Pericardium / Q000166:cytology*; D051381:Rats; D017208:Rats, Wistar; D058469:Receptors, Purinergic P2X / Q000235:genetics / Q000378:metabolism; D058470:Receptors, Purinergic P2Y / Q000235:genetics / Q000378:metabolism; D019063:Tenascin / Q000378:metabolism*
chemical_list: D016207:Cytokines; D058469:Receptors, Purinergic P2X; D058470:Receptors, Purinergic P2Y; D019063:Tenascin; D015720:5'-Nucleotidase; D000241:Adenosine
keywords: A2B receptor; IL-6; P2X7 receptor; inflammasome; mesenchymal cells