ATC Abstracts

American Transplant Congress abstracts

  • Home
  • Meetings Archive
    • 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
    • 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
  • Advanced Search

Tissue Inhibitor of Metalloproteinase-3 (TIMP-3) Protects Against Loss of Hepatic Integrity After Ischemia-Reperfusion Injury.

T. Fujii, S. Duarte, R. Busuttil, A. Coito.

Surgery, The Dumont-UCLA Transplant Center, Los Angeles, CA.

Meeting: 2016 American Transplant Congress

Abstract number: C97

Keywords: Ischemia, knockout, Leukocytes, Liver transplantation, Mice

Session Information

Date: Monday, June 13, 2016

Session Name: Poster Session C: Ischemia Reperfusion Injury and Organ Preservation

Session Time: 6:00pm-7:00pm

 Presentation Time: 6:00pm-7:00pm

Location: Halls C&D

Related Abstracts
  • AAV-Mediated TIMP-1 Gene Therapy Ameliorates Hepatic Ischemia/Reperfusion Injury
  • Anti-Inflammatory Effects of AAV-Mediated TIMP-1 Gene Transfer in Hepatic Ischemia-Reperfusion Injury.

Liver ischemia-reperfusion injury (IRI) remains a challenging problem in clinical orthotopic liver transplantation (OLT). Tissue inhibitor of metalloproteinases-3 (TIMP-3) is an extracellular matrix (ECM)-associated protein known to regulate metalloproteinases. Its expression has been linked to a variety of physiological and pathological functions, including regulation of inflammation. In this study we assessed the functional significance of TIMP-3 expression in a well-established mouse model of hepatic IRI. Methods: TIMP-3 deficient mice (TIMP-3 -/-) and matched wild-type (WT) control littermates were submitted to 60-min of partial warm ischemia followed by 6h of reperfusion. Results: TIMP-3 mRNA expression was detected in WT livers and absent in TIMP-3-/- livers. Compared to WT controls, TIMP-3-/- mice showed significantly higher AST (5,090±2,376 vs. 7.882±2895; p<0.05) and ALT (6,526±2548 vs. 12,493±4937; p<0.02) levels (IU/L) post-IRI. Overall, loss of TIMP-3 resulted in further lobular architecture disruption and severe necrosis after IRI. TIMP-3-/- livers showed significantly increased Mac-1 (32.4±11.2 vs. 57.9±13.4/HPF; p<0.005) and Ly6G (37.7±13.8 vs. 76.3±17.0/HPF; p<0.002) leukocyte infiltration and higher levels of pro-inflammatory cytokines, such as IL-1β (p<0.02), IL-6 (p<0.02) and TNF-α (p<0.01). Moreover, the inability of TIMP-3-/- mice to express TIMP-3 led to a significant loss of e-cadherin expression in the membranes of hepatocytes near the portal area. Indeed, while the full-length e-cadherin 120 kDa protein was readily detected in naïve (WT and TIMP-3-/-) livers and in WT livers post-IRI, it was significantly depressed in TIMP-3-/- livers after reperfusion (p<0.005). In contrast, the 35 kDa e-cadherin fragment was notably increased in TIMP-3-/- livers post-reperfusion (p<0.02), suggesting that TIMP-3 hampers e-cadherin shedding after liver IRI. Conclusion: Our results show for the first time that TIMP-3 deficiency results in enhanced leukocyte recruitment and liver damage after IRI. They also evidence a protective role for TIMP-3 in preventing the proteolytic cleavage of hepatic e-cadherin, an important mediator of intercellular adhesion and tissue integrity.

CITATION INFORMATION: Fujii T, Duarte S, Busuttil R, Coito A. Tissue Inhibitor of Metalloproteinase-3 (TIMP-3) Protects Against Loss of Hepatic Integrity After Ischemia-Reperfusion Injury. Am J Transplant. 2016;16 (suppl 3).

  • Tweet
  • Email
  • Print

To cite this abstract in AMA style:

Fujii T, Duarte S, Busuttil R, Coito A. Tissue Inhibitor of Metalloproteinase-3 (TIMP-3) Protects Against Loss of Hepatic Integrity After Ischemia-Reperfusion Injury. [abstract]. Am J Transplant. 2016; 16 (suppl 3). https://atcmeetingabstracts.com/abstract/tissue-inhibitor-of-metalloproteinase-3-timp-3-protects-against-loss-of-hepatic-integrity-after-ischemia-reperfusion-injury/. Accessed April 21, 2021.

« Back to 2016 American Transplant Congress

Most Viewed Abstracts

  • This Week
  • This Month
  • All Time
  • Subtherapeutic Low Tacrolimus Trough Levels (≤3.5 Ng /ml) Are A Risk Factor For Acute Rejection And Creatinine Doubling.
  • Low GFR after Kidney Donation Is Not Chronic Kidney Disease
  • Is There a Difference Between DCD and DBD Kidney Transplantation with Similar KDPI?
  • Penis Transplantation: First U.S. Experience.
  • Live Related Kidney Transplant Experience in Abuja, Nigeria – First Eight Cases Ever.
    • Assessment of Anti-A and Anti-B Antibody Titers in Different IVIG Preparations: Correlation with Risk for Hemolysis

    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 © 2013-2021 by American Society of Transplantation and the American Society of Transplant Surgeons. All rights reserved.

    Privacy Policy | Terms of Use

    loading Cancel
    Post was not sent - check your email addresses!
    Email check failed, please try again
    Sorry, your blog cannot share posts by email.
    This site uses cookies: Find out more.