Silencing of MiRNA-126 in Kidney Ischemia Reperfusion is Associated with Elevated SDF-1 Levels and Mobilization of Sca-1+/Lin- Progenitor Cells

Author(s): Roel Bijkerk, Coen van Solingen, Hetty C. de Boer, Dorottya K. de Vries, Matthieu Monge, Annemarie van Oeveren-Rietdijk, Eric P. van der Veer, Alexander F. Schaapherder, Ton J. Rabelink and Anton J. van Zonneveld

Volume 3 , Issue 3 , 2014

Page: [144 - 149] Pages: 6

DOI: 10.2174/2211536604666150121000340

Price: $65


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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