TGF-β/Smad signaling in the injured liver

被引：155

作者：

Breitkopf, K ^{[1
]}

Godoy, P ^{[1
]}

Ciuclan, L ^{[1
]}

Singer, MV ^{[1
]}

Dooley, S ^{[1
]}

机构：

[1] Heidelberg Univ, Klinikum Mannheim, Dept Med 2, Div Mol Alcohol Res Gastroenterol, Mannheim, Germany

来源：

ZEITSCHRIFT FUR GASTROENTEROLOGIE | 2006年 / 44卷 / 01期

关键词：

TGF-beta; smad; liver; fibrosis; HSC; EMT; interferon-gamma;

D O I：

10.1055/s-2005-858989

中图分类号：

R57 [消化系及腹部疾病];

学科分类号：

摘要：

TGF-beta, acting both directly and indirectly, represents a central mediator of fibrogenic remodeling processes in the liver. Besides hepatic stellate cells (HSCs), which are induced by TGF-beta to transdifferentiate to myofibroblasts and to produce extracellular matrix, hepatocytes are also strongly responsive for this cytokine, which induces apoptosis during fibrogenesis and provides growth control in regeneration processes. Based on this, TGF-beta-mediated hepatic responses to injury are the result of a complex interplay between the different liver cell types. In this review we summarize the knowledge about TGF-beta signal transduction in HSCs with special impact on Smad pathways. We further describe a molecular cross-talk between profibrogenic TGF-beta and antifibrogenic IFN-gamma signaling in liver cells. Finally, we introduce hepatocyte plasticity and epithelial-to-mesenchymal transition in the liver, which is well established in tumorigenesis, as a potential feature of fibrogenesis and highlight possible action points of TGF-beta in these contexts.

引用

页码：57 / 66

页数：10

共 75 条

[1] Perturbations of the AKT signaling pathway in human cancer [J].

Altomare, DA ;

Testa, JR .

ONCOGENE, 2005, 24 (50) :7455-7464

[2] Transgenic expression in the liver of truncated Met blocks apoptosis and permits immortalization of hepatocytes [J].

Amicone, L ;

Spagnoli, FM ;

Spath, G ;

Giordano, S ;

Tommasini, C ;

Bernardini, S ;

DeLuca, V ;

DellaRocca, C ;

Weiss, MC ;

Comoglio, PM ;

Tripodi, M .

EMBO JOURNAL, 1997, 16 (03) :495-503

[3] Phosphatidylinositol 3-kinase function is required for transforming growth factor β-mediated epithelial to mesenchymal transition and cell migration [J].

Bakin, AV ;

Tomlinson, AK ;

Bhowmick, NA ;

Moses, HL ;

Arteaga, CL .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2000, 275 (47) :36803-36810

[4] CELL-SPECIFIC EXPRESSION OF TRANSFORMING GROWTH-FACTOR-BETA IN RAT-LIVER - EVIDENCE FOR AUTOCRINE REGULATION OF HEPATOCYTE PROLIFERATION [J].

BISSELL, DM ;

WANG, SS ;

JARNAGIN, WR ;

ROLL, FJ .

JOURNAL OF CLINICAL INVESTIGATION, 1995, 96 (01) :447-455

[5] Transforming growth factor β and the liver [J].

Bissell, DM ;

Roulot, D ;

George, J .

HEPATOLOGY, 2001, 34 (05) :859-867

[6] A potent far-upstream enhancer in the mouse pro alpha 2(I) collagen gene regulates expression of reporter genes in transgenic mice [J].

BouGharios, G ;

Garrett, LA ;

Rossert, J ;

Niederreither, K ;

Eberspaecher, H ;

Smith, C ;

Black, C ;

deCrombrugghe, B .

JOURNAL OF CELL BIOLOGY, 1996, 134 (05) :1333-1344

[7]

BREIKOPF KHS, IN PRESS ACER

[8] Thrombospondin 1 acts as a strong promoter of transforming growth factor β effects via two distinct mechanisms in hepatic stellate cells [J].

Breitkopf, K ;

Sawitza, I ;

Westhoff, JH ;

Wickert, L ;

Dooley, S ;

Gressner, AM .

GUT, 2005, 54 (05) :673-681

[9] Early-onset multifocal inflammation in the transforming growth factor beta 1-null mouse is lymphocyte mediated [J].

Diebold, RJ ;

Eis, MJ ;

Yin, MY ;

Ormsby, I ;

Boivin, GP ;

Darrow, BJ ;

Saffitz, JE ;

Doetschman, T .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1995, 92 (26) :12215-12219

[10] Expression of Smads during in vitro transdifferentiation of hepatic stellate cells to myofibroblasts [J].

Dooley, S ;

Streckert, M ;

Delvoux, B ;

Gressner, AM .

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2001, 283 (03) :554-562

← 1 2 3 4 5 6 7 8 →