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- Title
Renoprotective effects of asialoerythropoietin in diabetic mice against ischaemia–reperfusion-induced acute kidney injury.
- Authors
NAKAZAWA, JUN; ISSHIKI, KEIJI; SUGIMOTO, TOSHIRO; ARAKI, SHIN-ICHI; KUME, SHINJI; YOKOMAKU, YUKIYO; CHIN-KANASAKI, MASAMI; SAKAGUCHI, MASAYOSHI; KOYA, DAISUKE; HANEDA, MASAKAZU; KASHIWAGI, ATSUNORI; UZU, TAKASHI
- Abstract
The renoprotective effects of asialoerythropoietin on acute kidney injury may be mediated through the induction of bcl-2 and BMP-7. Suppression of bcl-2 and BMP-7 could explain the acceleration of renal damage after ischemia-reperfusion injury in the diabetic kidney. Aim: Diabetic patients are at higher risk of failure to recover after acute kidney injury, however, the mechanism and therapeutic strategies remain unclear. Erythropoietin is cytoprotective in a variety of non-haematopoietic cells. The aim of the present study was to clarify the mechanism of diabetes-related acceleration of renal damage after ischaemia–reperfusion injury and to examine the therapeutic potential of asialoerythropoietin, a non-haematopoietic erythropoietin derivative, against ischaemia–reperfusion-induced acute kidney injury in diabetic mice. Methods: C57BL/6J mice with and without streptozotocin-induced diabetes were subjected to 30 min unilateral renal ischaemia–reperfusion injury at 1 week after induction of diabetes. They were divided into four group: (i) non-diabetic plus ischaemia–reperfusion injury; (ii) non-diabetic plus ischaemia–reperfusion injury plus asialoerythropoietin (3000 IU/kg bodyweight); (iii) diabetic plus ischaemia–reperfusion injury; and (iv) diabetic plus ischemia–reperfusion injury plus asialoerythropoietin. Experiments were conducted at the indicated time periods after ischaemia–reperfusion injury. Results: Ischaemia–reperfusion injury of diabetic kidney resulted in significantly low protein expression levels of bcl-2, an anti-apoptotic molecule, and bone morphogenetic protein-7 (BMP-7), an anti-fibrotic and pro-regenerative factor, compared with non-diabetic kidneys. Diabetic kidney subsequently showed severe damage including increased tubular cell apoptosis, tubulointerstitial fibrosis and decreased tubular proliferation, compared with non-diabetic kidney. Treatment with asialoerythropoietin induced bcl-2 and BMP-7 expression in diabetic kidney and decreased tubular cell apoptosis, tubulointerstitial fibrosis and accelerated tubular proliferation. Conclusion: Reduced induction bcl-2 and BMP-7 may play a role in the acceleration of renal damage after ischaemia–reperfusion injury in diabetic kidney. The renoprotective effects of asialoerythropoietin on acute kidney injury may be mediated through the induction of bcl-2 and BMP-7.
- Subjects
KIDNEY injuries; REPERFUSION injury; PEOPLE with diabetes; ERYTHROPOIETIN; ISCHEMIA treatment; THERAPEUTICS
- Publication
Nephrology, 2010, Vol 15, Issue 1, p93
- ISSN
1320-5358
- Publication type
Article
- DOI
10.1111/j.1440-1797.2009.01170.x