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.
Keywords: Ischemia-reperfusion injury, kidney injury, microRNA, miR-126, Sdf-1, Vegf-A, vascular progenitor cells.
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