Hematopoietic MicroRNA-126 protects against renal ischemia/reperfusion injury by promoting vascular integrity

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. StaalCees Van Kooten, Ton J. Rabelink, Anton Jan Van Zonneveld*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

90 Citations (Scopus)

Abstract

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 ofmiR-126 increases neovascularization of subcutaneously implanted Matrigel plugs in mice. After renal IRI, mice overexpressing miR-126 displayed amarked 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.

Original languageEnglish
Pages (from-to)1710-1722
Number of pages13
JournalJournal of the American Society of Nephrology
Volume25
Issue number8
DOIs
Publication statusPublished - Aug 2014

Bibliographical note

Publisher Copyright:
Copyright © 2014 by the American Society of Nephrology.

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