title: Protective effects of HBSP on ischemia reperfusion and cyclosporine a induced renal injury.
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.
authors.affiliation: Department of Pathology and Comparative Medicine Institute, University of Nantong, Nantong, Jiangsu 226001, China.
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Wu
authors.forename: Junlin
authors.initials: J
authors.lastname: Zhang
authors.forename: Feng
authors.initials: F
authors.lastname: Liu
authors.forename: Cheng
authors.initials: C
authors.lastname: Yang
authors.forename: Yufang
authors.initials: Y
authors.lastname: Zhang
authors.forename: Aifen
authors.initials: A
authors.lastname: Liu
authors.forename: Lan
authors.initials: L
authors.lastname: Shi
authors.forename: Yajun
authors.initials: Y
authors.lastname: Wu
authors.forename: Tongyu
authors.initials: T
authors.lastname: Zhu
authors.forename: Michael L
authors.initials: ML
authors.lastname: Nicholson
authors.forename: Yaping
authors.initials: Y
authors.lastname: Fan
authors.forename: Bin
authors.initials: B
authors.lastname: Yang
mesh_terms: D058186:Acute Kidney Injury / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D000818:Animals; D017209:Apoptosis; D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism; D016572:Cyclosporine / Q000009:adverse effects*; D004789:Enzyme Activation; D004921:Erythropoietin / Q000627:therapeutic use*; D005355:Fibrosis; D015870:Gene Expression; D007249:Inflammation / Q000473:pathology; D007668:Kidney / Q000473:pathology / Q000503:physiopathology; D007677:Kidney Function Tests; D008297:Male; D010446:Peptide Fragments / Q000627:therapeutic use*; D020011:Protective Agents / Q000627:therapeutic use*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D015427:Reperfusion Injury / Q000150:complications*
chemical_list: D010446:Peptide Fragments; D020011:Protective Agents; D012333:RNA, Messenger; C585201:glutaminyl-glutamyl-glutaminyl-leucyl-glutamyl-arginyl-alanyl-leucyl-asparagyl-seryl-serine; D004921:Erythropoietin; D016572:Cyclosporine; D053148:Caspase 3