Animal models for the study of liver fibrosis: new insights from knockout mouse models

被引:54
作者
Hayashi, Hiromitsu [1 ]
Sakai, Takao [1 ,2 ]
机构
[1] Cleveland Clin, Lerner Res Inst, Dept Biomed Engn, Cleveland, OH 44195 USA
[2] Cleveland Clin, Lerner Res Inst, Orthoped & Rheumatol Res Ctr, Cleveland, OH 44195 USA
来源
AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY | 2011年 / 300卷 / 05期
关键词
liver fibrogenesis; knockout mice; extracellular matrix; HEPATIC STELLATE CELLS; RENIN-ANGIOTENSIN SYSTEM; NECROSIS-FACTOR RECEPTOR; TGF-BETA; CARBON-TETRACHLORIDE; EXTRACELLULAR-MATRIX; TISSUE INHIBITOR; GENE-EXPRESSION; CONCANAVALIN-A; RAT-LIVER;
D O I
10.1152/ajpgi.00013.2011
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
Fibrosis arises as part of a would-healing response that maintains organ structure and integrity following tissue damage but also contributes to a variety of human pathologies such as liver fibrosis. Liver fibrosis is an abnormal response of the liver to persistent injury with the excessive accumulation of collagenous extracellular matrices. Currently there is no effective treatment, and many patients end up with a progressive form of the disease, eventually requiring a liver transplant. The clarification of mechanisms underlying pathogenesis of liver fibrosis and the development of effective therapy are of clinical importance. Experimental animal models, in particular targeted gene knockouts (loss of function) in mice, have become a powerful resource to address the molecular mechanisms or significance of the targeted gene in hepatic functions and diseases. This review will focus on the recent advances in knowledge obtained from genetically engineered mice that provide novel insights into the pathophysiology of liver fibrosis.
引用
收藏
页码:G729 / G738
页数:10
相关论文
共 124 条
[1]   The histological course of nonalcoholic fatty liver disease: a longitudinal study of 103 patients with sequential liver biopsies [J].
Adams, LA ;
Sanderson, S ;
Lindor, KD ;
Angulo, P .
JOURNAL OF HEPATOLOGY, 2005, 42 (01) :132-138
[2]  
Afford SC, 1998, J PATHOL, V186, P82, DOI 10.1002/(SICI)1096-9896(199809)186:1<82::AID-PATH151>3.0.CO
[3]  
2-D
[4]   Making sense of latent TGFβ activation [J].
Annes, JP ;
Munger, JS ;
Rifkin, DB .
JOURNAL OF CELL SCIENCE, 2003, 116 (02) :217-224
[5]  
Baker SJ, 1996, ONCOGENE, V12, P1
[6]   Tet repressor-based system for regulated gene expression in eukaryotic cells: Principles and advances [J].
Baron, U ;
Bujard, H .
APPLICATIONS OF CHIMERIC GENES AND HYBRID PROTEINS PT B: CELL BIOLOGY AND PHYSIOLOGY, 2000, 327 :401-421
[7]   Liver fibrosis [J].
Bataller, R ;
Brenner, DA .
JOURNAL OF CLINICAL INVESTIGATION, 2005, 115 (02) :209-218
[8]   Prolonged infusion of angiotensin II into normal rats induces stellate cell activation and proinflammatory events in liver [J].
Bataller, R ;
Gäbele, E ;
Schoonhoven, R ;
Morris, T ;
Lehnert, M ;
Yang, L ;
Brenner, DA ;
Rippe, RA .
AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY, 2003, 285 (03) :G642-G651
[9]   Angiotensin II induces contraction and proliferation of human hepatic stellate cells [J].
Bataller, R ;
Ginès, P ;
Nicolás, JM ;
Görbig, MN ;
Garcia-Ramallo, E ;
Gasull, X ;
Bosch, J ;
Arroyo, V ;
Rodés, J .
GASTROENTEROLOGY, 2000, 118 (06) :1149-1156
[10]   NADPH oxidase signal transduces angiotensin II in hepatic stellate cells and is critical in hepatic fibrosis [J].
Bataller, R ;
Schwabe, RF ;
Choi, YH ;
Yang, L ;
Paik, YH ;
Lindquist, J ;
Qian, T ;
Schoonhoven, R ;
Hagedorn, CH ;
Lemasters, JJ ;
Brenner, DA .
JOURNAL OF CLINICAL INVESTIGATION, 2003, 112 (09) :1383-1394