Postconditioning attenuates renal ischemia-reperfusion injury by mobilization of stem cells

J Nephrol. 2015 Jun;28(3):289-98. doi: 10.1007/s40620-015-0171-7. Epub 2015 Feb 6.

Abstract

Background: We recently showed that reactive oxygen species (ROS) and mitochondrial DNA damage and deletions were attenuated by postconditioning (POC). It is not known, however, whether a population of progenitor cells is recruited by POC and is responsible for repair of renal tubular epithelial cells after ischemic injury.

Methods: The model of renal POC was induced by 45 min clamping of the left renal artery and right nephrectomy followed by 7 min of short-time full reperfusion and 3 cycles of 30 s ischemia and 30 s reperfusion. The lymphocyte compartment of peripheral blood was evaluated by fluorescence-activated cell sorting (FACS) to determine expression of the bone marrow-derived progenitor cell markers CXC-chemokine receptor 4 (CXCR4), c-Kit, and CD34, at 12 h, 1 day and 3 days post-ischemia. Serum and kidney tissue were collected for analysis at 3 and 7 days post-ischemia.

Results: Renal functional and structural recovery was markedly improved by POC, which increased the number of CXCR4(+) and CD34(+) stem cells in peripheral blood and kidney tissue. Inhibition of ROS burst by POC was likely associated with increased hypoxia-inducible factor-1 expression, which may further promote stromal cell-derived factor 1 (SDF-1) expression.

Conclusions: The mechanisms of stem cell recruitment to the injured foci mobilized by POC appear to be mediated by moderate oxidative stress, which may lead to increased SDF-1 expression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Kidney Injury / genetics
  • Acute Kidney Injury / metabolism
  • Acute Kidney Injury / pathology
  • Acute Kidney Injury / physiopathology
  • Acute Kidney Injury / prevention & control*
  • Animals
  • Antigens, CD34 / metabolism
  • Biomarkers / metabolism
  • Cell Movement*
  • Chemokine CXCL12 / genetics
  • Chemokine CXCL12 / metabolism
  • Disease Models, Animal
  • Hematopoietic Stem Cell Mobilization / methods*
  • Hematopoietic Stem Cells / metabolism
  • Hematopoietic Stem Cells / pathology*
  • Hypoxia-Inducible Factor 1 / genetics
  • Hypoxia-Inducible Factor 1 / metabolism
  • Ischemic Postconditioning / methods*
  • Kidney Tubules / metabolism
  • Kidney Tubules / pathology*
  • Kidney Tubules / physiopathology
  • Male
  • Oxidative Stress
  • Proto-Oncogene Proteins c-kit / metabolism
  • RNA, Messenger / metabolism
  • Rats, Sprague-Dawley
  • Reactive Oxygen Species / metabolism
  • Receptors, CXCR4 / metabolism
  • Reperfusion Injury / genetics
  • Reperfusion Injury / metabolism
  • Reperfusion Injury / pathology
  • Reperfusion Injury / physiopathology
  • Reperfusion Injury / prevention & control*
  • Time Factors

Substances

  • Antigens, CD34
  • Biomarkers
  • CXCL12 protein, rat
  • Chemokine CXCL12
  • Cxcr4 protein, rat
  • Hypoxia-Inducible Factor 1
  • RNA, Messenger
  • Reactive Oxygen Species
  • Receptors, CXCR4
  • Proto-Oncogene Proteins c-kit