Macrophage infiltration and cellular proliferation in the non-ischemic kidney and heart following prolonged unilateral renal ischemia

Hirobumi Tokuyama, Darren J. Kelly, Yuan Zhang, Renae M. Gow, Richard E. Gilbert

Research output: Contribution to journalArticle

38 Citations (Scopus)

Abstract

Background/Aims: Although ischemic renal failure remains a major cause of morbidity and mortality, whether ischemic changes within a kidney might also have adverse effects on other organs has not been examined. Furthermore, given the protective effects of angiotensin II receptor (AT1) antagonism in renal ischemia, we considered whether a similar strategy might also modulate the response to acute renal insult. Methods: Unilateral renal artery ligation was performed in Sprague-Dawley rats, treated with or without the AT1 antagonist losartan (30 mg/kg/day). After 24 h of renal ischemia, changes in the contralateral kidney and heart were examined. Results: Contralateral non-ischemic kidneys displayed increased expression of platelet-derived growth factor-B (PDGF-B) in association with increased tubular cell proliferation. Gene expression for the macrophage chemokine osteopontin (OPN) was similarly increased along with substantial macrophage infiltration. In the heart, expression of OPN and macrophage numbers were increased. All of these changes, in both the heart and kidney were attenuated by losartan. Conclusion: Rather than affecting a single organ, the present study demonstrates that after prolonged renal ischemia, the contralateral kidney and heart undergo changes in growth factor and chemokine expression, resulting in pathological proliferation and inflammation that can be modulated by blockade of the AT1 receptor.

Original languageEnglish
Pages (from-to)54-62
Number of pages9
JournalNephron - Physiology
Volume106
Issue number3
DOIs
Publication statusPublished - 2007 Jul
Externally publishedYes

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Ischemia
Macrophages
Cell Proliferation
Kidney
Osteopontin
Losartan
Chemokines
Proto-Oncogene Proteins c-sis
Angiotensin Receptors
Renal Artery
Renal Insufficiency
Ligation
Sprague Dawley Rats
Intercellular Signaling Peptides and Proteins
Inflammation
Morbidity
Gene Expression
Mortality

Keywords

  • Epidermal growth factor
  • Osteopontin
  • Platelet-derived growth factor
  • Proliferating cell nuclear factor

ASJC Scopus subject areas

  • Physiology
  • Nephrology
  • Physiology (medical)

Cite this

Macrophage infiltration and cellular proliferation in the non-ischemic kidney and heart following prolonged unilateral renal ischemia. / Tokuyama, Hirobumi; Kelly, Darren J.; Zhang, Yuan; Gow, Renae M.; Gilbert, Richard E.

In: Nephron - Physiology, Vol. 106, No. 3, 07.2007, p. 54-62.

Research output: Contribution to journalArticle

Tokuyama, Hirobumi ; Kelly, Darren J. ; Zhang, Yuan ; Gow, Renae M. ; Gilbert, Richard E. / Macrophage infiltration and cellular proliferation in the non-ischemic kidney and heart following prolonged unilateral renal ischemia. In: Nephron - Physiology. 2007 ; Vol. 106, No. 3. pp. 54-62.
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