Copyright ©The Author(s) 2015.
World J Gastroenterol. Nov 14, 2015; 21(42): 12114-12124
Published online Nov 14, 2015. doi: 10.3748/wjg.v21.i42.12114
Table 1 Classification and characteristics of the main matrix metalloproteinases
MMP (class and number)NameExtracellular Matrix substrate
MMP-1Collagenase 1Collagen I, II, III, VII, VIII and X, gelatin, proteoglycans, tenascin, entactin
MMP-8Collagenase 2Collagen I, II, III, V, VIII and X, gelatin, aggrecan
MMP-13Collagenase 3Collagen I, II, III, IV, IX and X, fibronectin, gelatin, tenascin, aggrecan, osteonectin
MMP-2Gelatinase ACollagen I, IV, V, VII, IX and X, gelatin, proteoglycans, elastin, fibronectin, laminin, aggrecan, versican, osteonectin
MMP-9Gelatinase BCollagen IV, V, VII, X and XIV, gelatin, proteoglycans, elastin, aggrecan, versican, osteonectin
MMP-3Stromelysins 1Collagen III, IV, V, and IX, gelatin, proteoglycans, tenascin, fibronectin, laminin, aggrecan, versican, osteonectin
MMP-10Stromelysins 2Collagen III, IV and V, gelatin, proteoglycans, aggrecan, elastin, casein
MMP-11Stromelysins 3Collagen IV, fibronectin, laminin, gelatin, transferrin
Membrane type
MMP-14MT1-MMPCollagen I, II and III, fibronectin, vitronectin, tenascin, laminin, proteoglycans, aggrecan, elastin, casein, entactin
MMP-15MT2-MMPFibronectin, tenascin, laminin
MMP-16MT3-MMPCollagen III, fibronectin, casein, gelatin
MMP-24MT5-MMPActivator of proMMP-2
MMP-25MT6-MMPCollagen IV, fibronectin, gelatin, fibrinogen
MMP-7Collagen IV and X, gelatin, proteoglycans, tenascin, fibronectin, laminin, aggrecan, osteonectin, entactin, casein, tranferrin, integrin b4
MMP-12Collagen IV, gelatin, proteoglycans, fibronectin, laminin, entactin, casein, vibronectin, elastin
MMP-19NDAggrecan, cartilage oligomeric matrix protein (COMP)
MMP-26Matrilysin 2Collagen IV, fibronectin, casein, fibrinogen
Table 2 Synthetic compounds involved in matrix metalloproteinase regulation
CompoundsMechanism involvedMMPs involvedI/R modelRef.
BortezomibDownregulation of pro-inflammatory (IL-1β, TNF-α and IFN-γ) and pro-fibrotic (VEGF, TGF-β, HGF, bFGF) factorsMMP-2MMP-9Steatotic orthotopic liver transplantTiriveedhi et al[45],Transpl Immunol 2014
KMUP-1 (NO-donor)Protects from apoptosis-associated free radical generation and pro-inflammationMMP-9Hypoxic HepG2 cellsKuo et al[90], Int J Imm Pharm 2013
CS-1 peptideBlocks fibronectin α4β1 and decreases the release of pro-inflammatory mediatorsMMP-9MT-1-MMP/MMP-14Cold ischemiaDuarte et al[91],Am J Transpl 2012
CTT peptideReduction in TNF-α, IL-1, IL-2 and IFN-γMMP-9Acute small-for-size liver graftMa et al[34], Am J Transpl 2010
Cyclic RGD peptideDepresses inflammatory mediators (IFN-γ)MMP-9Steatotic Cold ischemiaFondevila et al[92],Am J Transpl 2009
ONO-1714iNOS inhibitorMMP-9Warm ischemiaHamada et al[46], Am J Pathol 2009
RXP409Inhibitory effects on MMP activityMMPsCold ischemiaDefamie et al[28],Hepatology 2008
Anti-MMP-9Decrease in expression of TNF-α, IL-2 and IFN-γMMP-9Warm ischemiaHamada et al[23], Hepatology 2008
CS-1 peptideBlocks FN α4β1 integrin and its FN ligandMMP-9Steatotic orthotopic liver transplantMoore et al[29], Am J Pathol 2007
ONO-4817Reduction in TNF-α, IL-1βMMP-2 and MMP-9Warm ischemiaShirahane et al[33],Surgery 2006
NACReduction in free radicalsMMP-9Warm ischemiaChen et al[93], Transpl Proc 2005
BB3103Prostaglandin PGE(1) protectionMMP-2Cold ischemiaYang et al[94], Microvasc Res 2002
RXPO3Protects from necrosis/apoptosisMMP-3-9-11-13Warm ischemiaCursio et al[24], FASEB J 2002
Table 3 Endogenous factors associated with matrix metalloproteinase modulation
FactorsMMPs InvolvedI/R ModelRef.
FN-α-β1MMP-9MT1-MMP/MMP-14Cold ischemiaDuarte et al[91], Am J Transpl 2012
Coito[48], Curr Opin Organ Transplant 2011
Moore et al[29], Am J Pathol 2007
Fondevilla et al[95], Transplant Proc 2005
Amersi et al[47], Am J Pathol 2003
Tenascin-CMMP-9Warm ischemiaKuriyama et al[96], Hepatology 2011
iNOSMMP-9Warm ischemiaHamada et al[46], Am J Pathol 2009
TNF-αMMP-2 and MMP-9Warm ischemiaFeng et al[39], J Surg Res 2013
Palladini et al[43], Toxicol and Pathol 2012
Khandoga et al[26], J Leukoc Biol 2006
Chen et al[93], Transplant Proc 2005
IL-1βMMP-2 and MMP-9Warm ischemiaShirahane et al[33], Surgery 2006
IL-6MMP-9Warm ischemiaHamada et al[46], Am J Pathol 2009
IFNα-2aMMP-2 and MMP-9CholestasisBueno et al[54], J Hepatol 2000
CD62MMP-2 and MMP-9Warm ischemiaKhandoga et al[26], J Leukoc Biol 2006
PlasminMMP-9CholestasisMartínez-Rizo et al[97], Liver Int 2010
TGF-βMMP-9Warm ischemiaFeng et al[39], J Surg Res 2013
MMP-13CholestasisAldaba-Muruato et al[98], Can J Physiol Pharmacol 2012
IL-10MMP-2 and MMP-9Warm ischemiaFeng et al[99], Int Immunopharmacol 2012