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.
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.
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.
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)
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Published online: April 24, 2008Associate Editor: A. Geerts
☆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.
© 2008 European Association for the Study of the Liver. Published by Elsevier Inc. All rights reserved.