title: The roles of lipocalin-2 in small-for-size fatty liver graft injury.
abstract: OBJECTIVE
  To investigate the roles and underlying mechanism of an inflammatory mediator-lipocalin-2 (Lcn2) in small-for-size fatty graft liver injury.
  
  
  BACKGROUND
  Understanding of the distinct mechanism regulating small-for-size fatty liver graft injury will be crucial to prevent marginal graft failure during living donor liver transplantation (LDLT).
  
  
  METHODS
  The roles of Lcn2 in small fatty graft injury were investigated in orthotopic liver transplantation model rats, human LDLT samples, an in vitro simulated ischemia-reperfusion (IR) model, and a hepatic ischemic reperfusion plus major hepatectomy (IR + H) model in mice.
  
  
  RESULTS
  Our result showed that Lcn2 was significantly upregulated together with elevation of chemokine (C-X-C motif) ligand 10 (CXCL10) and activation/infiltration of intragraft macrophages after liver transplantation using small-for-size fatty liver graft compared with that of using small-for-size normal liver graft. Intragraft and plasma levels of Lcn2 were intensified in patients who underwent transplantation with small-for-size fatty graft after LDLT. Lcn2 and CXCL10 were expressed higher in fatty hepatocytes after the simulated IR injury compared with normal hepatocytes. Overexpression of Lcn2 significantly deteriorated IR + H-induced hepatic injury in correlation with upregulation of CXCL10 and augmentation of infiltrated macrophages. On the contrary, hepatic injury of small fatty liver remnant after IR + H operation was attenuated in the Lcn-2 mice because of suppression of CXCL10 expression and diminishment of macrophage infiltration.
  
  
  CONCLUSIONS
  Lcn2 is an important regulator in small-for-size fatty liver graft injury and targeting Lcn2 may be feasible for preventing marginal graft failure in LDLT.
authors.affiliation: *Departments of Surgery and Centre for Cancer Research; and †Medicine, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong, China.
authors.forename: Qiao
authors.initials: Q
authors.lastname: Cheng
authors.forename: Kevin T P
authors.initials: KT
authors.lastname: Ng
authors.forename: Aimin
authors.initials: A
authors.lastname: Xu
authors.forename: Chang-Xian
authors.initials: CX
authors.lastname: Li
authors.forename: Xiao-Bing
authors.initials: XB
authors.lastname: Liu
authors.forename: Dong-Yong
authors.initials: DY
authors.lastname: Guo
authors.forename: Ronnie T P
authors.initials: RT
authors.lastname: Poon
authors.forename: Sheung-Tat
authors.initials: ST
authors.lastname: Fan
authors.forename: Chung-Mau
authors.initials: CM
authors.lastname: Lo
authors.forename: Kwan
authors.initials: K
authors.lastname: Man
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002460:Cell Line; D004247:DNA / Q000235:genetics*; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005234:Fatty Liver / Q000209:etiology / Q000235:genetics* / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D007150:Immunohistochemistry; D000071068:Lipocalin-2; D054834:Lipocalins / Q000096:biosynthesis / Q000235:genetics*; D008099:Liver / Q000378:metabolism / Q000473:pathology; D016031:Liver Transplantation; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D055031:Primary Graft Dysfunction / Q000150:complications* / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: C097278:Lcn2 protein, rat; D000071068:Lipocalin-2; D054834:Lipocalins; D004247:DNA