Background/Aims
ADAMs (A Disintegrin And Metalloprotease) are multifunctional, membrane-bound and
soluble cell surface glycoproteins with numerous functions in cell physiology. We
assessed the expression of ADAMs in fibrotic liver disease of different aetiologies
and clarified whether the expression of ADAMs is related to histological staging of
fibrosis. In addition, the expression of ADAMs was determined in different cell types
of liver.
Methods
Seventy-one biopsy samples from patients with chronic liver diseases were analyzed
for mRNA expression of ADAM-8, -9, -12, -28, -TS1, -TS2, matrix metalloprotease (MMP)-2,
-9 and tissue inhibitor of metalloproteinases-1 and -2 by quantitative real-time RT-PCR.
Results
The ADAM expression in liver injury is independent of aetiology. A strong correlation
between ADAM -9, -28, -TS1 versus MMP-2 and SMA was identified. Activated hepatic
stellate cells (HSC) showed increased mRNA expression of ADAM-8, -9, -12, -28, -TS2
compared to quiescent HSC. Significant differences between histological stages of
fibrosis were found for ADAM-28, MMP-2 and MMP-9.
Conclusions
The results suggest that ADAMs are differentially expressed in the liver. We assume
that ADAM-9, -TS1 and -TS2 play a crucial role in extracellular matrix remodeling
during fibrotic processes in the liver.
Abbreviations:
ADAM (A Disintegrin And Metalloproteinase), MMP (matrix metalloproteinase), ECM (extracellular matrix), TIMP (tissue inhibitor of metalloproteinases), HSC (hepatic stellate cells)Keywords
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References
- Extracellular matrix degradation and the role of hepatic stellate cells.Semin Liver Dis. 2001; 21: 737-784
- Matrix metalloproteinases.Curr Protoc Cell Biol. 2003; 10: 10
- Mechanisms of fibrinolysis in chronic liver injury (with special emphasis on MMPs and TIMPs).Z Gastroenterol. 2007; 45: 25-33
- FibrogenesisI: new insights into hepatic stellate cell activation: the simple become complex.Am J Physiol Gastrointest Liver Physiol. 2000; 279: G7-G11
- Activation of hepatic stellate cells-a key issue in liver fibrosis.Front Biosci. 2002; 7: d808-d826
- Evidence that tumor necrosis factor alpha converting enzyme is involved in regulated alpha-secretase cleavage of the Alzheimer amyloid protein precursor.J Biol Chem. 1998; 273: 27765-27767
- KUZ, a conserved metalloprotease–disintegrin protein with two roles in Drosophila neurogenesis.Science. 1996; 273: 1227-1231
- A metalloprotease–disintegrin participating in myoblast fusion.Nature. 1995; 377: 652-656
- A potential fusion peptide and an integrin ligand domain in a protein active in sperm–egg-fusion.Nature. 1992; 356: 248-252
- ADAM-12 protease induces adipogenesis in transgenic mice.Am J Pathol. 2002; 160: 1895-1903
- ADAM-mediated ectodomain shedding of HB-EGF in receptor cross-talk.Biochim Biophys Acta. 2005; 1751: 110-117
- Distinct roles for ADAM 10 and ADAM 17 in ectodomain shedding of six EGFR-ligands.J Cell Biol. 2004; 164: 769-779
- A secreted form of human ADAM-9 has α-secretase activity for APP.Biochem Biophys Res Commun. 2002; 293: 800-805
- Cloning and expression of ADAM-9 in Pichia pastoris catalytically active against fibronectin.Prot Exp Purif. 2001; 21: 65-70
- The in vitro activity of ADAM-10 is inhibited by TIMP-1 and TIMP-3.FEBS. 2000; 473: 275-279
- The enzymatic activity of ADAM-8 and ADAM-9 is not regulated by TIMPs.FEBS. 2002; 524: 154-158
- Increased mRNA expression of ADAMs in renal cell carcinoma and their association with clinical outcome.Oncol Rep. 2004; 11: 326-529
- Matrix metalloproteinase (MMP)-2, MMP-7, and tissue inhibitor of metalloproteinase-1 are closely related to fibroproliferative process in the liver during chronic hepatitis C.J Hepatol. 2001; 34: 239-247
- Purified rat liver fat-storing cells in culture divide and contain collagen.Heptology. 1984; 4: 392-403
- Large-scale isolation of human hepatocytes for therapeutic application.Cell Transplant. 2005; 14: 845-853
- A novel human metalloprotease synthesized in the liver and secreted into the blood: possibly, the von Willebrand factor-cleaving protease ?.J Biochem (Tokyo). 2001; 130: 475-480
- Increased ADAMTS-13 proteolytic activity in rat hepatic stellate cells upon activation in vitro and in vivo.J Thromb Haemost. 2006; 4: 1063-1070
- A secreted form of ADAM9 promotes carcinoma invasion through tumor-stromal interactions.Cancer Res. 2005; 65: 4728-4738
- ADAM, a novel family of membrane proteins containing A Disintegrin And Metalloprotease domain: multipotential functions in cell–cell and cell–matrix interactions.J Cell Biol. 1995; 131: 275-278
- Matrix-metalloproteinase-2 is an interstitial collagenase-inhibitor-free enzyme catalyzes the cleavage of collagen fibrils and soluble native type I collagen generating the specific 3/4- and 1/4 length fragments.J Biol Chem. 1995; 270: 5872-5876
- ADAM metallopeptidase with thrombospondin type 1 motif inactivation reduces the extent and stability of carbon tetrachloride-induced hepatic fibrosis in mice.Hepatology. 2007; 46: 1620-1631
- Localization of ADAMTS13 to the stellate cells of human liver.Blood. 2005; 106: 922-924
- ADAM12 in human liver cancers: TGF-β-regulated expression in stellate cells is associated with matrix remodeling.Hepatology. 2003; 37: 1056-1066
- Seminars in medicine of the Beth Israel Hospital Boston. The cellular basis of hepatic fibrosis, mechanisms and treatment strategies.N Engl J Med. 1993; 328: 1828-1835
- Matrix metalloproteinases in liver and serum in chronic active hepatitis C and HCV-induced cirrhosis.Hep Res. 1999; 14: 119-134
- The enzymatic activity of ADAM8 and ADAM9 is not regulated by TIMPs.FEBS Lett. 2002; 31: 154-158
- Tissue inhibitor of metalloproteinase-I and interstitial collagenase expression in autoimmune chronic active hepatitis and activated human hepatic lipocytes.Clin Sci. 1995; 89: 75-81
- Progelatinase A is produced and activated by rat hepatic stellate cells and promotes their proliferation.Hepatology. 1999; 30: 977-986
- MDC-L, a novel metalloprotease disintegrin cysteine-rich protein family member expressed by human lymphocytes.J Biol Chem. 1999; 274: 29251-29259
- Identification, sequence analysis and expression of transcripts encoding a putative metalloproteinase, eMDC II, in human and macaque epididymis.Mol Hum Reprod. 1999; 5: 1127-1134
- ADAM28 is overexpressed in human non-small cell lung carcinomas and correlates with cell proliferation and lymph node metastasis.Int J Cancer. 2006; 118: 263-273
- ADAM 28 is overexpressed in human breast carcinomas: implications for carcinoma cell proliferation through cleavage of insulin-like growth factor binding protein-3.Cancer Res. 2006; 66: 9913-9920
Article info
Publication history
Published online: April 24, 2008
Associate Editor: A. GeertsFootnotes
☆The authors who have taken part in the research of this paper declared that they do not have a relationship with the manufacturers of the materials involved either in the past or present and they did not receive funding from the manufacturers to carry out their research.
Identification
Copyright
© 2008 European Association for the Study of the Liver. Published by Elsevier Inc. All rights reserved.
