title: CXCL4 Contributes to the Pathogenesis of Chronic Liver Allograft Dysfunction.
abstract: Chronic liver allograft dysfunction (CLAD) remains the most common cause of patient morbidity and allograft loss in liver transplant patients. However, the pathogenesis of CLAD has not been completely elucidated. By establishing rat CLAD models, in this study, we identified the informative CLAD-associated genes using isobaric tags for relative and absolute quantification (iTRAQ) proteomics analysis and validated these results in recipient rat liver allografts. CXCL4, CXCR3, EGFR, JAK2, STAT3, and Collagen IV were associated with CLAD pathogenesis. We validated that CXCL4 is upstream of these informative genes in the isolated hepatic stellate cells (HSC). Blocking CXCL4 protects against CLAD by reducing liver fibrosis. Therefore, our results indicated that therapeutic approaches that neutralize CXCL4, a newly identified target of fibrosis, may represent a novel strategy for preventing and treating CLAD after liver transplantation.
authors.affiliation: Department of Anesthesiology, General Hospital of Tianjin Medical University, Tianjin 300052, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Critical Care Medicine, General Hospital of Tianjin Medical University, Tianjin 300052, China.
authors.forename: Bin
authors.identifier: 0000-0002-6956-546X
authors.initials: B
authors.lastname: Liu
authors.affiliation: Organ Transplantation Center, Tianjin First Center Hospital, Nankai District, Tianjin 300192, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Shi
authors.affiliation: Department of Anesthesiology, General Hospital of Tianjin Medical University, Tianjin 300052, China.
authors.forename: Ke-Liang
authors.initials: KL
authors.lastname: Xie
authors.affiliation: Department of Cell Biology and Research Center of Basic Medical Science, Tianjin Medical University, Qixiangtai Road, Heping District, Tianjin 300070, China.
authors.forename: Hai-Fang
authors.initials: HF
authors.lastname: Yin
authors.affiliation: Liver Transplantation Center, West China Hospital of Sichuan University, Chengdu 610041, Sichuan Province, China.
authors.forename: Lu-Nan
authors.initials: LN
authors.lastname: Yan
authors.affiliation: Faculty of Medicine, The Chinese University of Hong Kong, Prince of Wales Hospital, Sha Tin, Hong Kong.
authors.forename: Wan-Yee
authors.initials: WY
authors.lastname: Lau
authors.affiliation: Department of Anesthesiology, General Hospital of Tianjin Medical University, Tianjin 300052, China; Department of Critical Care Medicine, General Hospital of Tianjin Medical University, Tianjin 300052, China.
authors.forename: Guo-Lin
authors.initials: GL
authors.lastname: Wang
mesh_terms: D064591:Allografts / Q000503:physiopathology*; D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D004195:Disease Models, Animal; D055166:Hepatic Stellate Cells / Q000378:metabolism; D006801:Humans; D008099:Liver / Q000473:pathology; D008103:Liver Cirrhosis / Q000517:prevention & control; D008107:Liver Diseases / Q000235:genetics / Q000276:immunology / Q000503:physiopathology* / Q000628:therapy; D016031:Liver Transplantation; D010978:Platelet Factor 4 / Q000097:blood / Q000235:genetics* / Q000276:immunology / Q000378:metabolism*; D040901:Proteomics; D051381:Rats; D054367:Receptors, CXCR3 / Q000235:genetics / Q000378:metabolism; D014184:Transplantation, Homologous
chemical_list: D000911:Antibodies, Monoclonal; C515189:Cxcr3 protein, rat; D054367:Receptors, CXCR3; D010978:Platelet Factor 4