IJCEM Copyright © 2008-All rights reserved. Published by e-Century Publishing Corporation, Madison, WI 53711
Int J Clin Exp Med 2010;3(2):180-185

Original Article
Modulation of matrix metalloproteinase-9 and tissue inhibitor of matrix
metalloproteinase-1 in sepsis

Subir R. Maitra, Asha Jacob, Mian Zhou, Ping Wang

Department of Surgery, North Shore University Hospital and Long Island Jewish Medical Center; and The Feinstein Institute for Medical
Research Manhasset, NY 11030, USA

Received May 21, 2010, accepted June 8, 2010, available online June 12, 2010

Abstract: Previous studies demonstrated that hepatic matrix metalloproteinase-9 (MMP-9) activity increased following cecal ligation
and puncture (CLP) in rats, indicating liver injury in sepsis. The activity of MMP-9 in degrading extracellular matrix is controlled by
activation of proenzymes and inhibition of tissue inhibitor of MMPs (TIMP-1).  To further assess the proteolytic cascade imbalance in
sepsis, hepatic MMP-9 and TIMP-1 expressions were examined in CLP rats.  In this study, sepsis was induced in rats by CLP, and at
10 and 20 h after sepsis induction, liver samples were collected and MMP-2, MMP-9, and TIMP-1 gene and protein expressions were
evaluated by real time PCR and Western blot analysis, respectively.  Gene expression of MMP-9 was increased by 6.4-fold and 3.0-fold
at 10 h and 20 h after CLP as compared to sham group, respectively.  Likewise, MMP-9 protein expression was also significantly
increased at both time points. In contrast, MMP-2 gene expression was not altered at 10 h and 20 h after CLP as compared to sham
controls. Interestingly, TIMP-1 gene expression was elevated to 89-fold and 46-fold from sham levels at 10 h and 20 h after CLP,
respectively. Similarly, TIMP-1 protein levels were also significantly increased at both time points. In addition, MMP-9/TIMP-1 protein
ratio was lower at both 10 h and 20 h after CLP compared to sham rats. Results demonstrated an imbalance between MMP and TIMP,
with a more evident role for MMP-9 than MMP-2, and high value of TIMP-1 was particularly evident in CLP rats. Our results indicate that
MMP-9 and TIMP-1 expressions are increased and they may serve as useful markers to predict the outcome of sepsis.
(IJCEM1005003).

Key words: TIMP-1, sepsis, MMP-9/TIMP-1 ratio, MMP-2

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Address all correspondence to:
Ping Wang, MD
Laboratory of Surgical Research
The Feinstein Institute for Medical Research
350 Community Drive
Manhasset, NY 11030
Tel: (516) 562-3411
Fax: (516) 562-1022
Email: pwang@nshs.edu