Integrin-TGF-β crosstalk in fibrosis, cancer and wound healing

被引:494
作者
Margadant, Coert [1 ]
Sonnenberg, Arnoud [1 ]
机构
[1] Netherlands Canc Inst, Div Cell Biol, NL-1066 CX Amsterdam, Netherlands
关键词
integrin; TGF-beta; fibrosis; cancer; wound healing; GROWTH-FACTOR-BETA; EPITHELIAL-MESENCHYMAL TRANSITION; ACTIVATES LATENT TGF-BETA-1; RECEPTOR KINASE INHIBITOR; HUMAN LUNG FIBROBLASTS; ALPHA-V-BETA-6; INTEGRIN; INCREASED EXPRESSION; PULMONARY-FIBROSIS; IN-VIVO; TRANSFORMING GROWTH-FACTOR-BETA-1;
D O I
10.1038/embor.2009.276
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Accumulating evidence indicates that there is extensive crosstalk between integrins and TGF-beta signalling. TGF-beta affects integrin-mediated cell adhesion and migration by regulating the expression of integrins, their ligands and integrin-associated proteins. Conversely, several integrins directly control TGF-beta activation. In addition, a number of integrins can interfere with both Smad-dependent and Smad-independent TGF-beta signalling in different ways, including the regulation of the expression of TGF-beta signalling pathway components, the physical association of integrins with TGF-beta receptors and the modulation of downstream effectors. Reciprocal TGF-beta-integrin signalling is implicated in normal physiology, as well as in a variety of pathological processes including systemic sclerosis, idiopathic pulmonary fibrosis, chronic obstructive pulmonary disease and cancer; thus, integrins could provide attractive therapeutic targets to interfere with TGF-beta signalling in these processes.
引用
收藏
页码:97 / 105
页数:9
相关论文
共 77 条
[1]   The αvβ6 integrin plays a role in compromised epidermal wound healing [J].
AlDahlawi, Salwa ;
Eslami, Ameneh ;
Hakkinen, Lari ;
Larjava, Hannu S. .
WOUND REPAIR AND REGENERATION, 2006, 14 (03) :289-297
[2]   Mice that lack activity of αvβ6-and αvβ8-integrins reproduce the abnormalities of Tgfb1- and Tgfb3-null mice [J].
Aluwihare, Poshala ;
Mu, Zhenyu ;
Zhao, Zhicheng ;
Yu, Dawen ;
Weinreb, Paul H. ;
Horan, Gerald S. ;
Violette, Shelia M. ;
Munger, John S. .
JOURNAL OF CELL SCIENCE, 2009, 122 (02) :227-232
[3]  
Amendt C, 2002, J CELL SCI, V115, P2189
[4]   Integrin αvβ6-mediated activation of latent TGF-β requires the latent TGF-β binding protein-1 [J].
Annes, JP ;
Chen, Y ;
Munger, JS ;
Rifkin, DB .
JOURNAL OF CELL BIOLOGY, 2004, 165 (05) :723-734
[5]   Squamous metaplasia amplifies pathologic epithelial-mesenchymal interactions in COPD patients [J].
Araya, Jun ;
Cambier, Stephanie ;
Markovics, Jennifer A. ;
Wolters, Paul ;
Jablons, David ;
Hill, Arthur ;
Finkbeiner, Walter ;
Jones, Kirk ;
Broaddus, V. Courtney ;
Sheppard, Dean ;
Barzcak, Andrea ;
Xiao, Yuanyuan ;
Erle, David J. ;
Nishimura, Stephen L. .
JOURNAL OF CLINICAL INVESTIGATION, 2007, 117 (11) :3551-3562
[6]   Integrin-mediated transforming growth factor-β activation regulates homeostasis of the pulmonary epithelial-mesenchymal trophic unit [J].
Araya, Jun ;
Cambier, Stephanie ;
Morris, Alanna ;
Finkbeiner, Walter ;
Nishimura, Stephen L. .
AMERICAN JOURNAL OF PATHOLOGY, 2006, 169 (02) :405-415
[7]   Increased expression of integrin αvβ5 induces the myofibroblastic differentiation of dermal fibroblasts [J].
Asano, Y ;
Ihn, H ;
Yamane, K ;
Jinnin, M ;
Tamaki, K .
AMERICAN JOURNAL OF PATHOLOGY, 2006, 168 (02) :499-510
[8]   Increased expression of integrin αvβ3 contributes to the establishment of autocrine TGF-β signaling in scleroderma fibroblasts [J].
Asano, Y ;
Ihn, H ;
Yamane, K ;
Jinnin, M ;
Mimura, Y ;
Tamaki, K .
JOURNAL OF IMMUNOLOGY, 2005, 175 (11) :7708-7718
[9]   Involvement of αVβ5 integrin-mediated activation of latent transforming growth factor β1 in autocrine transforming growth factor β signaling in systemic sclerosis fibroblasts [J].
Asano, Y ;
Ihn, H ;
Yamane, K ;
Jinnin, M ;
Mimura, Y ;
Tamaki, K .
ARTHRITIS AND RHEUMATISM, 2005, 52 (09) :2897-2905
[10]   Involvement of αvβ5 integrin in the establishment of autocrine TGF-β signaling in dermal fibroblasts derived from localized scleroderma [J].
Asano, Yoshihide ;
Ihn, Hironobu ;
Jinnin, Masatoshi ;
Mimura, Yoshihiro ;
Tamaki, Kunihiko .
JOURNAL OF INVESTIGATIVE DERMATOLOGY, 2006, 126 (08) :1761-1769