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Updated: Aug 10, 2026
Renal Ischaemia Reperfusion Injury: A Mouse Model of Injury and Regeneration
Published on: June 7, 2014
Midkine antisense oligodeoxyribonucleotide inhibits renal damage induced by ischemic reperfusion
Waichi Sato1, Yoshifumi Takei, Yukio Yuzawa
1Department of Clinical Immunology of Internal Medicine, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Background:
Midkine, a heparin-binding growth factor, is involved in the migration of inflammatory cells. The inflammatory cell migration to the tubulointerstitium of the kidney after ischemia/reperfusion (I/R) injury is attenuated in midkine gene-deficient mice, resulting in better preservation of the tubulointerstitium compared with wild-type mice. In the present investigation, we planned to evaluate the usefulness of antisense midkine for the therapy of ischemic renal failure.
Methods:
Midkine antisense phosphorothioate oligodeoxyribonucleotide (ODN) at a dose of 1 mg/kg in saline was intravenously administered to mice 1 day before or after I/R. The kidneys were removed for examination 1, 2, 3, and 7 days after I/R.
Results:
It was rapidly incorporated into proximal tubular epithelial cells, and inhibited midkine synthesis, leading to reduced migration of inflammatory cells to the injured epithelial layer. Consequently, the midkine antisense ODN-treated animals exhibited less severe renal damage than untreated or midkine sense ODN-treated animals 2 days after I/R as assessed by morphologic criteria and blood urea nitrogen (BUN) and serum creatinine levels. Midkine expression, BUN, and serum creatinine levels were not significantly different between injection of midkine antisense ODN before and after ischemic injury.
Conclusion:
These results indicate that intravenous injection of midkine antisense ODN is a candidate for a novel therapeutic strategy against acute tubulointerstitial injury induced by I/R injury.
Insights
Midkine antisense oligodeoxynucleotides (ODN) reduce inflammatory cell migration and kidney damage following ischemia/reperfusion (I/R) injury. This therapeutic strategy shows promise for treating acute tubulointerstitial injury.
Area of Science:
- Nephrology
- Molecular Biology
- Immunology
Background:
- Midkine, a growth factor, promotes inflammatory cell migration.
- Inhibition of midkine in gene-deficient mice attenuates kidney injury after ischemia/reperfusion (I/R).
Purpose of the Study:
- To evaluate midkine antisense oligodeoxynucleotides (ODN) as a therapy for ischemic renal failure.
Main Methods:
- Mice received intravenous midkine antisense ODN 1 day before or after I/R.
- Kidney tissues were examined at 1, 2, 3, and 7 days post-I/R.
Main Results:
- Midkine antisense ODN reduced midkine synthesis and inflammatory cell migration.
- Treated animals showed less renal damage, lower BUN and creatinine levels compared to controls.
- Timing of ODN administration (pre- or post-I/R) did not significantly alter outcomes.
Conclusions:
- Intravenous midkine antisense ODN is a potential therapeutic strategy for acute tubulointerstitial injury from I/R.
- This approach offers a novel treatment for ischemic renal failure.
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