title: Silencing of miRNA-126 in kidney ischemia reperfusion is associated with elevated SDF-1 levels and mobilization of Sca-1+/Lin- progenitor cells.
abstract: Integrity of the capillary network in the kidney is essential in the recovery from ischemia/ reperfusion injury (IRI), a phenomenon central to kidney transplantation and acute kidney injury. MicroRNA- 126 (miR-126) is known to be important in maintaining vascular homeostasis by facilitating vascular regeneration and modulating the mobilization of vascular progenitor cells. Stromal cell-derived factor 1 (SDF-1), important in the mobilization of vascular progenitor cells, is a direct target of miR-126 and modulation of miR-126 was previously shown to affect the number of circulating Sca-1(+)/Lin(-) vascular progenitor cells in a mouse model for hind limb ischemia. Here, we assessed the in vivo contribution of miR-126 to progenitor cell mobilization and kidney function following IRI in mice. A three day follow up of blood urea levels following kidney IRI demonstrated that systemic antagomir silencing of miR-126 did not impact the loss or subsequent restoration of kidney function. However, whole kidney lysates displayed elevated gene expression levels of Sdf-1, Vegf-A and eNOS after IRI as a result of systemic silencing of miR-126. Furthermore, FACS-analysis on whole blood three days after surgery revealed a marked up regulation of the number of circulating Sca-1(+)/Lin(-) progenitor cells in the antagomir-126 treated mice, in an ischemia dependent manner. Our data indicate that silencing of miR-126 can enhance renal expression of Sdf-1 after IRI, leading to the mobilization of vascular progenitor cells into the circulation.
authors.forename: Roel
authors.initials: R
authors.lastname: Bijkerk
authors.forename: Coen
authors.initials: C
authors.lastname: van Solingen
authors.forename: Hetty C
authors.initials: HC
authors.lastname: de Boer
authors.forename: Dorottya K
authors.initials: DK
authors.lastname: de Vries
authors.forename: Matthieu
authors.initials: M
authors.lastname: Monge
authors.forename: Annemarie
authors.initials: A
authors.lastname: van Oeveren-Rietdijk
authors.forename: Eric P
authors.initials: EP
authors.lastname: van der Veer
authors.forename: Alexander F
authors.initials: AF
authors.lastname: Schaapherder
authors.forename: Ton J
authors.initials: TJ
authors.lastname: Rabelink
authors.affiliation: Department of Nephrology, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, The Netherlands.
authors.forename: Anton J
authors.initials: AJ
authors.lastname: van Zonneveld
mesh_terms: D000818:Animals; D000950:Antigens, Ly / Q000235:genetics / Q000378:metabolism*; D054377:Chemokine CXCL12 / Q000235:genetics / Q000378:metabolism*; D066026:Endothelial Progenitor Cells / Q000166:cytology / Q000378:metabolism*; D020868:Gene Silencing; D007668:Kidney / Q000098:blood supply / Q000378:metabolism*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D052250:Nitric Oxide Synthase Type III / Q000235:genetics / Q000378:metabolism; D015427:Reperfusion Injury / Q000378:metabolism*; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism
chemical_list: D000950:Antigens, Ly; D054377:Chemokine CXCL12; C515256:Cxcl12 protein, mouse; C074650:Ly6a protein, mouse; C545201:MIRN126 microRNA, mouse; D008565:Membrane Proteins; D035683:MicroRNAs; D042461:Vascular Endothelial Growth Factor A; D052250:Nitric Oxide Synthase Type III