Midkine antisense oligodeoxyribonucleotide inhibits renal damage induced by ischemic reperfusion

Waichi Sato, Yoshifumi Takei, Yukio Yuzawa, Seiichi Matsuo, Kenji Kadomatsu, Takashi Muramatsu

Research output: Contribution to journalArticle

38 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)1330-1339
Number of pages10
JournalKidney International
Volume67
Issue number4
DOIs
Publication statusPublished - 01-01-2005
Externally publishedYes

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Antisense Oligodeoxyribonucleotides
Reperfusion
Kidney
Cell Movement
Blood Urea Nitrogen
Reperfusion Injury
Creatinine
midkine
Oligodeoxyribonucleotides
Wounds and Injuries
Serum
Intravenous Injections
Renal Insufficiency
Heparin
Intercellular Signaling Peptides and Proteins

All Science Journal Classification (ASJC) codes

  • Nephrology

Cite this

Sato, Waichi ; Takei, Yoshifumi ; Yuzawa, Yukio ; Matsuo, Seiichi ; Kadomatsu, Kenji ; Muramatsu, Takashi. / Midkine antisense oligodeoxyribonucleotide inhibits renal damage induced by ischemic reperfusion. In: Kidney International. 2005 ; Vol. 67, No. 4. pp. 1330-1339.
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Midkine antisense oligodeoxyribonucleotide inhibits renal damage induced by ischemic reperfusion. / Sato, Waichi; Takei, Yoshifumi; Yuzawa, Yukio; Matsuo, Seiichi; Kadomatsu, Kenji; Muramatsu, Takashi.

In: Kidney International, Vol. 67, No. 4, 01.01.2005, p. 1330-1339.

Research output: Contribution to journalArticle

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T1 - Midkine antisense oligodeoxyribonucleotide inhibits renal damage induced by ischemic reperfusion

AU - Sato, Waichi

AU - Takei, Yoshifumi

AU - Yuzawa, Yukio

AU - Matsuo, Seiichi

AU - Kadomatsu, Kenji

AU - Muramatsu, Takashi

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N2 - 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.

AB - 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.

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