title: The hormone melatonin stimulates renoprotective effects of "early outgrowth" endothelial progenitor cells in acute ischemic kidney injury.
abstract: Endothelial progenitor cells (EPCs) protect the kidney from acute ischemic injury. The aim of this study was to analyze whether pretreatment of murine "early outgrowth" EPCs (eEPCs) with the hormone melatonin increases the cells' renoprotective effects in the setting of murine acute ischemic renal failure. Male (8-12 wk old) C57Bl/6N mice were subjected to unilateral ischemia-reperfusion injury postuninephrectomy (40 min). Postischemic animals were injected with either 0.5×10(6) untreated syngeneic murine eEPCs or with cells, pretreated with melatonin for 1 h. Injections were performed shortly after reperfusion of the kidney. While animals injected with untreated cells developed acute renal failure, eEPC pretreatment with melatonin dramatically improved renoprotective actions of the cells. These effects were completely reversed after cell pretreatment with melatonin and the MT-1/-2 antagonist luzindole. In vitro analysis revealed that melatonin reduced the amount of tumor growth factor-β-induced eEPC apoptosis/necrosis. Secretion of vascular endothelial growth factor by the cells was markedly stimulated by the hormone. In addition, migratory activity of eEPCs was enhanced by melatonin and supernatant from melatonin-treated eEPCs stimulated migration of cultured mature endothelial cells. In summary, melatonin was identified as a new agonist of eEPCs in acute ischemic kidney injury.
authors.affiliation: Abteilung für Nephrologie und Rheumatologie, Universitätsklinikum Göttingen, Robert-Koch-Strasse 40, 37077 Göttingen, Germany. d.patschan@gmail.com
authors.forename: D
authors.initials: D
authors.lastname: Patschan
authors.forename: A
authors.initials: A
authors.lastname: Hildebrandt
authors.forename: J
authors.initials: J
authors.lastname: Rinneburger
authors.forename: J T
authors.initials: JT
authors.lastname: Wessels
authors.forename: S
authors.initials: S
authors.lastname: Patschan
authors.forename: J U
authors.initials: JU
authors.lastname: Becker
authors.forename: E
authors.initials: E
authors.lastname: Henze
authors.forename: A
authors.initials: A
authors.lastname: Krüger
authors.forename: G A
authors.initials: GA
authors.lastname: Müller
mesh_terms: D058186:Acute Kidney Injury / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000166:cytology*; D008297:Male; D008550:Melatonin / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009336:Necrosis; D018919:Neovascularization, Physiologic / Q000187:drug effects; D020127:Recovery of Function / Q000187:drug effects; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D013234:Stem Cells / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D016212:Transforming Growth Factor beta / Q000378:metabolism
chemical_list: D000975:Antioxidants; D016212:Transforming Growth Factor beta; D008550:Melatonin