Abstract |
Ischemia reperfusion (IR) and cyclosporine A (CsA) injuries are unavoidable in kidney transplantation and are associated with allograft dysfunction. Herein, the effect and mechanism of a novel tissue protective peptide, helix B surface peptide (HBSP) derived from erythropoietin, were investigated in a rat model. The right kidney was subjected to 45 min ischemia, followed by left nephrectomy and 2-week reperfusion, with or without daily treatment of CsA 25 mg/kg and/or HBSP 8 nmol/kg. Blood urea nitrogen was increased by CsA but decreased by HBSP at 1 week and 2 weeks, while the same changes were revealed in urinary protein/ creatinine only at 2 weeks. HBSP also significantly ameliorated tubulointerstitial damage and interstitial fibrosis, which were gradually increased by IR and CsA. In addition, apoptotic cells, infiltrated inflammatory cells, and active caspase-3+ cells were greatly reduced by HBSP in the both IR and IR + CsA groups. The 17 kD active caspase-3 protein was decreased by HBSP in the IR and IR + CsA kidneys, with decreased mRNA only in the IR + CsA kidneys. Taken together, it has been demonstrated, for the first time, that HBSP effectively improved renal function and tissue damage caused by IR and/or CsA, which might be through reducing caspase-3 activation and synthesis, apoptosis, and inflammation.
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Authors | Yuanyuan Wu, Junlin Zhang, Feng Liu, Cheng Yang, Yufang Zhang, Aifen Liu, Lan Shi, Yajun Wu, Tongyu Zhu, Michael L Nicholson, Yaping Fan, Bin Yang |
Journal | Clinical & developmental immunology
(Clin Dev Immunol)
Vol. 2013
Pg. 758159
( 2013)
ISSN: 1740-2530 [Electronic] Egypt |
PMID | 24282430
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Peptide Fragments
- Protective Agents
- RNA, Messenger
- glutaminyl-glutamyl-glutaminyl-leucyl-glutamyl-arginyl-alanyl-leucyl-asparagyl-seryl-serine
- Erythropoietin
- Cyclosporine
- Caspase 3
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Topics |
- Acute Kidney Injury
(etiology, pathology, physiopathology, prevention & control)
- Animals
- Apoptosis
- Caspase 3
(genetics, metabolism)
- Cyclosporine
(adverse effects)
- Enzyme Activation
- Erythropoietin
(therapeutic use)
- Fibrosis
- Gene Expression
- Inflammation
(pathology)
- Kidney
(pathology, physiopathology)
- Kidney Function Tests
- Male
- Peptide Fragments
(therapeutic use)
- Protective Agents
(therapeutic use)
- RNA, Messenger
(genetics, metabolism)
- Rats
- Reperfusion Injury
(complications)
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