• Roel Bijkerk, Coen van Solingen, Hetty C de Boer, Pieter van der Pol, Meriem Khairoun, Ruben G de Bruin, Annemarie M van Oeveren-Rietdijk, Ellen Lievers, Nicole Schlagwein, Danielle J van Gijlswijk, Marko K Roeten, Zeinab Neshati, Antoine A F de Vries, Mark Rodijk, Karin Pike-Overzet, Yascha W van den Berg, Eric P van der Veer, Henri H Versteeg, Marlies E J Reinders, Frank J T Staal, Cees van Kooten, Ton J Rabelink, and Anton Jan van Zonneveld.
• Department of Nephrology, Einthoven Laboratory for Experimental Vascular Medicine.
• J. Am. Soc. Nephrol. 2014 Aug 1;25(8):1710-22.

AbstractIschemia/reperfusion injury (IRI) is a central phenomenon in kidney transplantation and AKI. Integrity of the renal peritubular capillary network is an important limiting factor in the recovery from IRI. MicroRNA-126 (miR-126) facilitates vascular regeneration by functioning as an angiomiR and by modulating mobilization of hematopoietic stem/progenitor cells. We hypothesized that overexpression of miR-126 in the hematopoietic compartment could protect the kidney against IRI via preservation of microvascular integrity. Here, we demonstrate that hematopoietic overexpression of miR-126 increases neovascularization of subcutaneously implanted Matrigel plugs in mice. After renal IRI, mice overexpressing miR-126 displayed a marked decrease in urea levels, weight loss, fibrotic markers, and injury markers (such as kidney injury molecule-1 and neutrophil gelatinase-associated lipocalin). This protective effect was associated with a higher density of the peritubular capillary network in the corticomedullary junction and increased numbers of bone marrow-derived endothelial cells. Hematopoietic overexpression of miR-126 increased the number of circulating Lin(-)/Sca-1(+)/cKit(+) hematopoietic stem and progenitor cells. Additionally, miR-126 overexpression attenuated expression of the chemokine receptor CXCR4 on Lin(-)/Sca-1(+)/cKit(+) cells in the bone marrow and increased renal expression of its ligand stromal cell-derived factor 1, thus favoring mobilization of Lin(-)/Sca-1(+)/cKit(+) cells toward the kidney. Taken together, these results suggest overexpression of miR-126 in the hematopoietic compartment is associated with stromal cell-derived factor 1/CXCR4-dependent vasculogenic progenitor cell mobilization and promotes vascular integrity and supports recovery of the kidney after IRI.Copyright © 2014 by the American Society of Nephrology.

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