ATC Abstracts

American Transplant Congress abstracts

  • Home
  • Meetings Archive
    • 2022 American Transplant Congress
    • 2021 American Transplant Congress
    • 2020 American Transplant Congress
    • 2019 American Transplant Congress
    • 2018 American Transplant Congress
    • 2017 American Transplant Congress
    • 2016 American Transplant Congress
    • 2015 American Transplant Congress
    • 2013 American Transplant Congress
  • Keyword Index
  • Resources
    • 2021 Resources
    • 2016 Resources
      • 2016 Welcome Letter
      • ATC 2016 Program Planning Committees
      • ASTS Council 2015-2016
      • AST Board of Directors 2015-2016
    • 2015 Resources
      • 2015 Welcome Letter
      • ATC 2015 Program Planning Committees
      • ASTS Council 2014-2015
      • AST Board of Directors 2014-2015
      • 2015 Conference Schedule
  • Search

The Liver X Receptor Alpha (LXRα) Knockout Protect Liver Against Ischemia-Reperfusin Injury in Mice

T. Lu,1 D. Li,1 J. Zhang,1 M. Zhang,1 X. Cui,1 H. Dai,1 X. Liu,2 Q. Xia.1

1Liver Surgery and Liver Transplantation Center, Renji Hospital, Shanghai, China
2Cardiovascular, Shanghai First People's Hospital, Shanghai, China.

Meeting: 2015 American Transplant Congress

Abstract number: D73

Keywords: Hepatocytes, Ischemia, Liver

Session Information

Session Name: Poster Session D: Innate Immunity in Transplantation

Session Type: Poster Session

Date: Tuesday, May 5, 2015

Session Time: 5:30pm-6:30pm

 Presentation Time: 5:30pm-6:30pm

Location: Exhibit Hall E

Background: Liver X Receptor Alpha (LXRα) is a transcription factor crucial for cholesterol, fatty acid, and glucose homeostasis. We hypothesize that LXRαKO may promote hepatocellular survival by promoting the hepatic antioxidant stress via the LXRα-fibroblast growth factor 21 (FGF21) pathway. Methods&Results: In our murine model of liver warm ischemia (90min) and reperfusion (0-12h), LXRαexpression peaked at 2h of reperfusion. Indeed, LXRα KO mice were resistant against liver IRI, as shown by sALT levels (3903±743U/L vs.7401±1080U/L in controls, p<0.0001) and liver histology, compared with WT controls. In parallel, intrahepatic expression of TNF-α, IL-1β, IL-6 and CXCL-10 were decreased in LXRαKO. We then assessed LXRαoverexpression (Adenovirus vector with LXRαgene) vs. WT livers (Adenovirus vector only) subjected to IR insult. Interestingly, hepatic LXRαoverexpression enhanced local injury, evidenced by increased sALT levels (14078±802U/Lvs.10220±877U/L in controls, p<0.01). Bone marrow transplantation was performed between the LXRαKO and WT mice.The LXRαKO recipients (WT⇒LXRαKO) have no significance with the other group of recipients (LXRαKO⇒LXRαKO), indicating that the LXRαKO plays an important role in the hepatocytes. We then focused on FGF21, the antioxidant stress downstream factor.The serum FGF21 was measured by ELISA,at 1h of reperfusion,the serum FGF21 was higher in LXRαKO IR-livers, as compared with WT controls (654±50U/Lvs.436±33U/L,p<0.001). To mimic in vivo settings, we used hydrogen peroxide (H2O2)-necrotic hepatocytes. Consistently, LXRαKO prevented H2O2-mediated hepatocyte necrosis in primary hepatocyte cultures in vitro. The cytoprotective effects of LXRαKO on hepatocytes were confirmed by decreased cytoplasmic LDH release, increased of FGF21. In contrast, addition of FGF21 SiRNA reversed LXRαKO-induced hepatocellular protection in vitro.Finally,intravenous of recombinant mouse FGF21 reversed LXRαoverexpression -induced hepatic injury in vivo.

Conclusion: This is the first study to provide evidence that LXRαKO may: 1) attenuate hepatocellular damage in pathophysiology of liver IRI; 2) enhance FGF21 expression; 3) exert cytoprotrotection via integrated LXRα-FGF21 signaling network in hepatocyte. These findings identify LXRα as a novel regulator of hepatocyte survival in a therapeutic regimen against organ IRI in transplant recipients.

  • Tweet
  • Click to email a link to a friend (Opens in new window) Email
  • Click to print (Opens in new window) Print

To cite this abstract in AMA style:

Lu T, Li D, Zhang J, Zhang M, Cui X, Dai H, Liu X, Xia Q. The Liver X Receptor Alpha (LXRα) Knockout Protect Liver Against Ischemia-Reperfusin Injury in Mice [abstract]. Am J Transplant. 2015; 15 (suppl 3). https://atcmeetingabstracts.com/abstract/the-liver-x-receptor-alpha-lxr-knockout-protect-liver-against-ischemia-reperfusin-injury-in-mice/. Accessed May 31, 2025.

« Back to 2015 American Transplant Congress

Visit Our Partner Sites

American Transplant Congress (ATC)

Visit the official site for the American Transplant Congress »

American Journal of Transplantation

The official publication for the American Society of Transplantation (AST) and the American Society of Transplant Surgeons (ASTS) »

American Society of Transplantation (AST)

An organization of more than 3000 professionals dedicated to advancing the field of transplantation. »

American Society of Transplant Surgeons (ASTS)

The society represents approximately 1,800 professionals dedicated to excellence in transplantation surgery. »

Copyright © 2013-2025 by American Society of Transplantation and the American Society of Transplant Surgeons. All rights reserved.

Privacy Policy | Terms of Use | Cookie Preferences