Metalloproteinases in liver fibrosis: current insights

Figures & data

Table 1 Hepatic toxins used in animal models

Inducer	Toxic metabolite	Mechanism	References
CCL4	Carbon trichloride radical	Lipid peroxidation and membrane damage	Weber et al^Citation111
TAA	Thioacetamide-S-oxide radical	Carbonyl moiety of TAA is bound to protein, protein damage	Porter and Neal^Citation112
Nitrosamines:	Diazonium ions	DNA alkylation	Kroeger-Koepke et al^Citation113
DEN
DMN
APAP	N-acetyl-p-benzoquinone imine	Oxidative conjugation with proteins and DNA	Jaeschke et al^Citation114
HFD	–	Accumulation of fat in liver	Lieber et al^Citation25
MCD diet	–	Low beta-oxidation, oxidative stress and inflammation	Anstee and Goldin^Citation115

Abbreviations: CCl₄, carbon tetrachloride; TAA, thioacetamide; DEN, diethylnitrosamine; DMN, dimethylnitrosamine; APAP, acetaminophen; HFD, high-fat diet; MCD diet, a diet deprived of methionine and choline.

Table 2 List of genes involved in spontaneous liver damage

Gene	Disease/pathology	Reference
NOD.c3c4	Primary biliary cirrhosis	Koarada et al,^Citation116 Mauad et al^Citation117
Mrd2	Cholestasis	Mauad et al,^Citation117 Oude Elferink et al,^Citation118 Smit et al,^Citation119 Fickert et al^Citation120
IL-2Rα	Primary biliary cirrhosis	Wakabayashi et al^Citation121
dnTGF-βRII	Primary biliary cirrhosis	Oertelt et al^Citation122
Ae2a,b	Primary biliary cirrhosis	Salas et al^Citation123
KK Ay/a	Steatosis/NAFLD	Okumura et al^Citation124
AlbCre Adam10	Cholestasis/Fibrosis	Müller et al^Citation78
PTEN	Steatosis/NASH	Horie et al^Citation125

Abbreviations: NAFLD, nonalcoholic fatty liver disease; NASH, nonalcoholic steatohepatitis.

Table 3 MMPs and TIMPs involved in mouse fibrosis

Treatment	Metalloproteinases and TIMP involved	Reference
Carbon tetrachloride	MMP-2, MMP-8, MMP-9, MMP-13, MMP-19, TIMP-1, TIMP-2	Jirouskova et al,^Citation65 Chung et al,^Citation126 Jiang et al,^Citation127 Marsillach et al^Citation128
Thioacetamide	MMP-2, MMP-12, TIMP-1, TIMP-2	Park et al,^Citation129 Chen et al^Citation130
Nitrosamines	MMP-2, MMP-9, MMP-13, TIMP-1, TIMP-2	Chen et al,^Citation130 Subramanian and Arul,^Citation131 Prakobwong et al,^Citation132 Mandal et al^Citation133
Acetaminophen	MMP-2, MMP-9	Ito et al^Citation134
High-fat diet	MMP-9, MMP-12,	Kato et al,^Citation135 Stanton et al,^Citation136
	MMP-13, TIMP-1,	de Meijer et al,^Citation137
	ADAM17	Wang et al^Citation138
MCD diet	MMP-2, MMP-9,	Lee et al,^Citation139 Wang et al,^Citation140
	MMP-13	Velayudham et al^Citation141
BDL	MMP-2, MMP-8,	Uchinami et al,^Citation142 Buryova
	MMP-9, MMP-13,	et al,^Citation143 Popov et al,^Citation144
	ADAM17, TIMP-1	Schrading et al,^Citation145 Diaz-Gil et al,^Citation146 Kossakowska et al^Citation147
DDC diet	MMP-2, MMP-9,	Chalupsky et al,^Citation106 Ishikawa
	ADAM17, ADAM10	et al^Citation148
Concanavalin A	MMP-2, MMP-9,	Arthur,^Citation7 Wang
	ADAM17	et al,^Citation37 Maeda et al,^Citation149 Okazaki et al^Citation150

Abbreviations: MMP, matrix metalloproteinase; TIMP, tissue inhibitor of metalloproteinase; ADAM, a disintegrin and metalloproteinase; BDL, bile duct ligation; DDC, 5-diethoxycarbonyl-1,4-dihydrocollidine; MCD diet, a diet deprived of methionine and choline.

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