Cited 60 times since 2014 (5.9 per year) source: EuropePMC Journal of the American Society of Nephrology : JASN, Volume 25, Issue 8, 7 1 2014, Pages 1710-1722 Hematopoietic microRNA-126 protects against renal ischemia/reperfusion injury by promoting vascular integrity. Bijkerk R, van Solingen C, de Boer HC, van der Pol P, Khairoun M, de Bruin RG, van Oeveren-Rietdijk AM, Lievers E, Schlagwein N, van Gijlswijk DJ, Roeten MK, Neshati Z, de Vries AA, Rodijk M, Pike-Overzet K, van den Berg YW, van der Veer EP, Versteeg HH, Reinders ME, Staal FJ, van Kooten C, Rabelink TJ, van Zonneveld AJ
Ischemia/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.
