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: Qiao Cheng, Kevin T P Ng, Aimin Xu, Chang-Xian Li, Xiao-Bing Liu, Dong-Yong Guo, Ronnie T P Poon, Sheung-Tat Fan, Chung-Mau Lo, Kwan Man
• Journal: Annals of surgery (Ann Surg) Vol. 260 Issue 6 Pg. 1062-72 (Dec 2014) ISSN: 1528-1140 [Electronic] United States
• PMID: 24374540 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Lcn2 protein, rat
• Lipocalin-2
• Lipocalins
• DNA

Topics

• Animals
• Blotting, Western
• Cell Line
• DNA (genetics)
• Disease Models, Animal
• Enzyme-Linked Immunosorbent Assay
• Fatty Liver (etiology, genetics, metabolism)
• Gene Expression Regulation
• Humans
• Immunohistochemistry
• Lipocalin-2
• Lipocalins (biosynthesis, genetics)
• Liver (metabolism, pathology)
• Liver Transplantation
• Male
• Mice
• Mice, Inbred C57BL
• Primary Graft Dysfunction (complications, genetics, metabolism)
• Rats
• Rats, Sprague-Dawley
• Reverse Transcriptase Polymerase Chain Reaction