title: Expression of hemopexin in acute rejection of rat liver allograft identified by serum proteomic analysis.
abstract: Acute rejection (AR) and acceptance of allograft after liver transplantation (LTx) remain critical issues that need addressing to improve prognosis. We therefore performed rat orthotopic LTx and proteomic analyses to screen for immune response-related biomarkers in sera. Markers identified were validated at the mRNA and/or protein levels, and the molecules of interest were functionally explored. Compared with syngeneic controls, signs of AR as well as spontaneous acceptance were observed in hematoxylin and eosin-stained sections of liver allografts. In accordance with the severity of AR, 30 protein spots displaying significant changes in abundance were identified using two-dimensional differential gel electrophoresis. Ultimately, 14 serum proteins were sequenced and five spots of interest were identified as hemopexin (HPX). Expression of HPX was significantly and inversely associated with the severity of AR at both the mRNA and protein levels. In vitro, Mt-1, Ho-1, Fth, Ifn-γ, and Il-17 transcripts were significantly upregulated in lysates of lymphocytes stimulated with HPX, whereas Il-10 markedly was remarkably downregulated. Interferon-γ, IL-10, and IL-17 proteins in the supernatant of HPX-stimulated lymphocytes were significantly altered in keeping with the mRNA level. Our data facilitated the generation of a proteomic profile to enhance the understanding of rat liver AR. In view of finding that the HPX serum level is negatively associated with the severity of AR of rat liver allograft, we propose that in vitro treatment with HPX regulates cytokine expression in rat lymphocytes.
authors.affiliation: *Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China; †Departments of General and Visceral Surgery, and ‡Gastroenterology and Endocrinology, University Medical Center Goettingen, Goettingen, Germany; and §Department of Surgery, Fujian Provincial Tumor Hospital, Teaching Hospital of Fujian Medical University, Fuzhou; and ∥Shanghai Key Laboratory of Organ Transplantation, Zhongshan Hospital, Fudan University, Shanghai, China.
authors.forename: Min
authors.initials: M
authors.lastname: Xu
authors.forename: Changjun
authors.initials: C
authors.lastname: Tan
authors.forename: Jinwu
authors.initials: J
authors.lastname: Hu
authors.forename: Salamah Mohammad
authors.initials: SM
authors.lastname: Alwahsh
authors.forename: Jun
authors.initials: J
authors.lastname: Yan
authors.forename: Jie
authors.initials: J
authors.lastname: Hu
authors.forename: Zhi
authors.initials: Z
authors.lastname: Dai
authors.forename: Zheng
authors.initials: Z
authors.lastname: Wang
authors.forename: Jian
authors.initials: J
authors.lastname: Zhou
authors.forename: Jia
authors.initials: J
authors.lastname: Fan
authors.forename: Xiaowu
authors.initials: X
authors.lastname: Huang
mesh_terms: D000208:Acute Disease; D000818:Animals; D015415:Biomarkers / Q000097:blood; D049109:Cell Proliferation / Q000187:drug effects; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation / Q000187:drug effects / Q000276:immunology; D006084:Graft Rejection / Q000235:genetics / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D006466:Hemopexin / Q000008:administration & dosage / Q000096:biosynthesis* / Q000235:genetics / Q000494:pharmacology; D008099:Liver / Q000378:metabolism / Q000473:pathology; D016031:Liver Transplantation; D008213:Lymphocyte Activation / Q000187:drug effects; D007959:Lymphocyte Culture Test, Mixed; D008214:Lymphocytes / Q000276:immunology; D008297:Male; D040901:Proteomics / Q000379:methods; D012333:RNA, Messenger / Q000235:genetics; D011916:Rats, Inbred F344; D011917:Rats, Inbred Lew; D014158:Transcription, Genetic
chemical_list: D015415:Biomarkers; D016207:Cytokines; D012333:RNA, Messenger; D006466:Hemopexin