title: Proteome Analysis of Renoprotection Mediated by a Novel Cyclic Helix B Peptide in Acute Kidney Injury.
abstract: We developed a novel, erythropoietin-derived, non-erythropoiesis, cyclic helix B peptide (CHBP) that displays potent renoprotection against acute kidney injury (AKI). To determine the mechanism of CHBP-mediated protection, we investigated the proteomic profile of mice treated with CHBP in a kidney ischemia-reperfusion (IR) injury model. The isobaric tags for relative and absolute quantitation (iTRAQ)-labeled samples were analyzed using a QSTAR XL LC/MS system. In total, 38 differentially expressed proteins (DEPs) were shared by all experimental groups, while 3 DEPs were detected specifically in the IR + CHBP group. Eight significant pathways were identified, and oxidative phosphorylation was shown to be the most important pathway in CHBP-mediated renoprotection. The significant DEPs in the oxidative phosphorylation pathway elicited by CHBP are NADH-ubiquinone oxidoreductase Fe-S protein 6 (NDUFS6), alpha-aminoadipic semialdehyde synthase (AASS) and ATP-binding cassette sub-family D member 3 (ABCD3). The DEPs mentioned above were verified by RT-qPCR and immunostaining in mouse kidneys. We tested 6 DEPs in human biopsy samples from kidney transplant recipients. The trend of differential expression was consistent with that in the murine model. In conclusion, this study helps to elucidate the pharmacological mechanisms of CHBP before clinical translation.
authors.affiliation: Department of Urology, Zhongshan Hospital, Fudan University, Shanghai, 200032, China.|Shanghai Key Laboratory of Organ Transplantation, Shanghai, 200032, China.|Department of Plastic Surgery, Zhongshan Hospital, Fudan University, Shanghai, 200032, China.
authors.forename: Cheng
authors.initials: C
authors.lastname: Yang
authors.affiliation: Department of Stomatology, Huashan Hospital, Fudan University, Shanghai, 200040, China.
authors.forename: Junjun
authors.initials: J
authors.lastname: Liu
authors.affiliation: Shanghai Key Laboratory of Organ Transplantation, Shanghai, 200032, China.
authors.forename: Long
authors.initials: L
authors.lastname: Li
authors.affiliation: Shanghai Key Laboratory of Organ Transplantation, Shanghai, 200032, China.|Biomedical Research Center, Zhongshan Hospital, Fudan University, Shanghai, 200032, China.
authors.forename: Meiyu
authors.initials: M
authors.lastname: Hu
authors.affiliation: CAS Key Laboratory of Receptor Research, Shanghai Institute of Material Medical, Chinese Academy of Sciences, Shanghai, 200032, China.
authors.forename: Yaqiu
authors.initials: Y
authors.lastname: Long
authors.affiliation: Department of Chemistry /Institutes of Biomedical Science, Fudan University, Shanghai, 200433, China.
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Urology, Zhongshan Hospital, Fudan University, Shanghai, 200032, China.|Shanghai Key Laboratory of Organ Transplantation, Shanghai, 200032, China.
authors.forename: Tongyu
authors.initials: T
authors.lastname: Zhu
authors.affiliation: Translational Center for Stem Cell Research, Tongji Hospital, Tongji University School of Medicine, Shanghai, 200065, China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Huang
authors.affiliation: Department of Stomatology, Huashan Hospital, Fudan University, Shanghai, 200040, China.
authors.forename: Shouliang
authors.initials: S
authors.lastname: Zhao
authors.affiliation: Department of Stomatology, Huashan Hospital, Fudan University, Shanghai, 200040, China.
authors.forename: Shangfeng
authors.initials: S
authors.lastname: Liu
authors.affiliation: Department of Urology, Zhongshan Hospital, Fudan University, Shanghai, 200032, China.|Shanghai Key Laboratory of Organ Transplantation, Shanghai, 200032, China.|Department of Transfusion, Zhongshan Hospital, Fudan University, Shanghai, 200032, China.
authors.forename: Ruiming
authors.initials: R
authors.lastname: Rong
mesh_terms: D058186:Acute Kidney Injury / Q000378:metabolism*; D000818:Animals; D004745:Enkephalins / Q000378:metabolism*; D004921:Erythropoietin / Q000378:metabolism; D007668:Kidney / Q000378:metabolism*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009243:NAD / Q000378:metabolism; D010085:Oxidative Phosphorylation; D011498:Protein Precursors / Q000378:metabolism*; D020543:Proteome / Q000378:metabolism*; D040901:Proteomics / Q000379:methods; D015427:Reperfusion Injury / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology
chemical_list: D004745:Enkephalins; D011498:Protein Precursors; D020543:Proteome; C056943:peptide B; D009243:NAD; D004921:Erythropoietin