Expression of MMPs and TIMPs in liver fibrosis – a systematic review with special emphasis on anti-fibrotic strategies  Stefanie Hemmann, Jürgen Graf, Martin Roderfeld, Elke Roeb  Journal of Hepatology  Volume 46, Issue 5, Pages 955-975 (May 2007) DOI: 10.1016/j.jhep.2007.02.003 Copyright © 2007 European Association for the Study of the Liver Terms and Conditions

Fig. 1 Domain organization of different mammalian MMPs. GPI (glycosylphosphatidylinositol) membrane anchor. Journal of Hepatology 2007 46, 955-975DOI: (10.1016/j.jhep.2007.02.003) Copyright © 2007 European Association for the Study of the Liver Terms and Conditions

Fig. 2 Mechanism of MMP inhibition by TIMP-1. (A) Structure of MMP-3 (yellow) showing the binding cleft in which the catalytic zinc ion (orange circle) is bound to three His in the active site. One coordination site of the zinc ion is occupied by a water molecule (not shown). Thus, permitting substrate binding. (B) TIMP-1 (blue) bound to active MMP-3 demonstrating the perfect structural fit of the two proteins. (C) Zoom into the active centre of MMP-3. Substrate binding of MMP-3 is inhibited by TIMP-1. N-terminal Cys1 amino group occupies the 4th coordination site of the zinc ion in the active centre. Graphics were generated based on PDB Database Entry No. 1UEA using PyMOL Software (www.pymol.org) [187]. Journal of Hepatology 2007 46, 955-975DOI: (10.1016/j.jhep.2007.02.003) Copyright © 2007 European Association for the Study of the Liver Terms and Conditions

Fig. 3 Possible expression profiles of MMPs and TIMPs incorporating the current knowledge of the pathophysiology of chronic toxic liver injury. Differences in y-axis values are arbitrarily set for better understanding. Journal of Hepatology 2007 46, 955-975DOI: (10.1016/j.jhep.2007.02.003) Copyright © 2007 European Association for the Study of the Liver Terms and Conditions

Fig. 4 Results of the systematic literature retrieval process via PubMed (refer to the text for the detailed search strategy). The number and reasons for study exclusion are given. Journal of Hepatology 2007 46, 955-975DOI: (10.1016/j.jhep.2007.02.003) Copyright © 2007 European Association for the Study of the Liver Terms and Conditions