PMID- 21898491
OWN - NLM
STAT- MEDLINE
DCOM- 20120207
LR  - 20211020
IS  - 1527-3350 (Electronic)
IS  - 0270-9139 (Print)
IS  - 0270-9139 (Linking)
VI  - 54
IP  - 6
DP  - 2011 Dec
TI  - Tenascin-C: a novel mediator of hepatic ischemia and reperfusion injury.
PG  - 2125-36
LID - 10.1002/hep.24639 [doi]
AB  - Hepatic ischemia/reperfusion (IRI) injury remains a major challenge in clinical 
      orthotopic liver transplantation (OLT). Tenascin-C (Tnc) is an extracellular 
      matrix protein (ECM) involved in various aspects of immunity and tissue injury. 
      Using a Tnc-deficient mouse model, we present data that suggest an active role 
      for Tnc in liver IRI. We show that Tnc-deficient mice have a reduction in liver 
      damage and a significant improvement in liver regeneration after IRI. The 
      inability of Tnc(-/-) mice to express Tnc significantly reduced the levels of 
      active caspase-3/transferase-mediated dUTP nick end-labeling (TUNEL) apoptotic 
      markers and enhanced the expression of the proliferation cell nuclear antigen 
      (PCNA) after liver IRI. The lack of Tnc expression resulted in impaired leukocyte 
      recruitment and decreased expressions of interleukin (IL)-1beta, IL-6, and CXCL2 
      after liver reperfusion. Tnc-deficient livers were characterized by altered 
      expression patterns of vascular adhesion molecules, such as vascular cell 
      adhesion molecule-1 and platelet endothelial cell adhesion molecule-1 post-IRI. 
      Moreover, matrix metalloproteinase-9 (MMP-9) synthesis, which facilitates 
      leukocyte transmigration across vascular barriers in liver IRI, was markedly 
      down-regulated in the absence of Tnc. We also show that Tnc is capable of 
      inducing MMP-9 expression in isolated neutrophils through Toll-like receptor 4. 
      Therefore, our data suggest that Tnc is a relevant mediator of the pathogenic 
      events underlying liver IRI. The data also support the view that studies aimed at 
      further understanding how newly synthesized ECM molecules, such as Tnc, 
      participate in inflammatory responses are needed to improve therapeutic 
      approaches in liver IRI.
CI  - Copyright (c) 2011 American Association for the Study of Liver Diseases.
FAU - Kuriyama, Naohisa
AU  - Kuriyama N
AD  - Dumont-UCLA Transplant Center, Division of Liver and Pancreas Transplantation, 
      Department of Surgery, David Geffen School of Medicine at UCLA, Los Angeles, CA 
      90095-7054, USA.
FAU - Duarte, Sergio
AU  - Duarte S
FAU - Hamada, Takashi
AU  - Hamada T
FAU - Busuttil, Ronald W
AU  - Busuttil RW
FAU - Coito, Ana J
AU  - Coito AJ
LA  - eng
GR  - R01 AI057832/AI/NIAID NIH HHS/United States
GR  - R01 AI057832-07/AI/NIAID NIH HHS/United States
GR  - R01 AI057832-08/AI/NIAID NIH HHS/United States
GR  - R01AI057832/AI/NIAID NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Hepatology
JT  - Hepatology (Baltimore, Md.)
JID - 8302946
RN  - 0 (Interleukin-1beta)
RN  - 0 (Interleukin-6)
RN  - 0 (Platelet Endothelial Cell Adhesion Molecule-1)
RN  - 0 (Tenascin)
RN  - 0 (Tlr4 protein, mouse)
RN  - 0 (Toll-Like Receptor 4)
RN  - 0 (Vascular Cell Adhesion Molecule-1)
RN  - 126547-89-5 (Intercellular Adhesion Molecule-1)
RN  - EC 3.4.22.- (Caspase 3)
RN  - EC 3.4.24.35 (Matrix Metalloproteinase 9)
SB  - IM
MH  - Animals
MH  - Caspase 3/metabolism
MH  - In Situ Nick-End Labeling
MH  - Intercellular Adhesion Molecule-1/biosynthesis
MH  - Interleukin-1beta/biosynthesis
MH  - Interleukin-6/biosynthesis
MH  - Liver/pathology/physiology
MH  - Liver Regeneration/*physiology
MH  - Matrix Metalloproteinase 9/biosynthesis
MH  - Mice
MH  - Platelet Endothelial Cell Adhesion Molecule-1/biosynthesis
MH  - Reperfusion Injury/*immunology
MH  - Tenascin/*deficiency/immunology
MH  - Toll-Like Receptor 4/physiology
MH  - Vascular Cell Adhesion Molecule-1/biosynthesis
PMC - PMC3230719
MID - NIHMS321655
EDAT- 2011/09/08 06:00
MHDA- 2012/02/09 06:00
PMCR- 2012/12/01
CRDT- 2011/09/08 06:00
PHST- 2011/09/08 06:00 [entrez]
PHST- 2011/09/08 06:00 [pubmed]
PHST- 2012/02/09 06:00 [medline]
PHST- 2012/12/01 00:00 [pmc-release]
AID - 10.1002/hep.24639 [doi]
PST - ppublish
SO  - Hepatology. 2011 Dec;54(6):2125-36. doi: 10.1002/hep.24639.