KLF2-induced actin shear fibers control both alignment to flow and JNK signaling in vascular endothelium

被引:78
作者
Boon, Reinier A. [1 ,2 ]
Leyen, Thomas A. [1 ]
Fontijn, Ruud D. [1 ]
Fledderus, Joost O. [2 ]
Baggen, Josefien M. C. [1 ]
Volger, Oscar L. [1 ,2 ]
Amerongen, Geerten P. van Nieuw [3 ]
Horrevoets, Anton J. G. [1 ]
机构
[1] Vrije Univ Amsterdam, Med Ctr, Dept Mol Cell Biol & Immunol, NL-1081 BT Amsterdam, Netherlands
[2] Univ Amsterdam, Acad Med Ctr, Dept Med Biochem, NL-1105 AZ Amsterdam, Netherlands
[3] Vrije Univ Amsterdam, Med Ctr, Dept Physiol, NL-1081 BT Amsterdam, Netherlands
关键词
KRUPPEL-LIKE FACTOR-2; FOCAL ADHESION KINASE; NECROSIS-FACTOR-ALPHA; TRANSCRIPTION FACTOR; HEMODYNAMIC FORCES; KLF2; EXPRESSION; STRESS FIBERS; ACTIVATION; INHIBITION; CELLS;
D O I
10.1182/blood-2009-06-228726
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
The shear stress-induced transcription factor Kruppel-like factor 2 (KLF2) confers antiinflammatory properties to endothelial cells through the inhibition of activator protein 1, presumably by interfering with mitogen-activated protein kinase (MAPK) cascades. To gain insight into the regulation of these cascades by KLF2, we used antibody arrays in combination with time-course mRNA microarray analysis. No gross changes in MAPKs were detected; rather, phosphorylation of actin cytoskeleton-associated proteins, including focal adhesion kinase, was markedly repressed by KLF2. Furthermore, we demonstrate that KLF2-mediated inhibition of Jun NH2-terminal kinase (JNK) and its downstream targetsATF2/c-Jun is dependent on the cytoskeleton. Specifically, KLF2 directs the formation of typical short basal actin filaments, termed shear fibers by us, which are distinct from thrombinor tumor necrosis factor-alpha-induced stress fibers. KLF2 is shown to be essential for shear stress-induced cell alignment, concomitant shear fiber assembly, and inhibition of JNK signaling. These findings link the specific effects of shear-induced KLF2 on endothelial morphology to the suppression of JNK MAPK signaling in vascular homeostasis via novel actin shear fibers. (Blood. 2010; 115: 2533-2542)
引用
收藏
页码:2533 / 2542
页数:10
相关论文
共 55 条
[1]   Hemizygous deficiency of Kruppel-like factor 2 augments experimental atherosclerosis [J].
Atkins, G. Brandon ;
Wang, Yunmei ;
Mahabeleshwar, Ganapati H. ;
Shi, Hong ;
Gao, Huiyun ;
Kawanami, Daiji ;
Natesan, Viswanath ;
Lin, Zhiyong ;
Simon, Daniel I. ;
Jain, Mukesh K. .
CIRCULATION RESEARCH, 2008, 103 (07) :690-693
[2]   Role of Kruppel-like transcription factors in endothelial biology [J].
Atkins, G. Brandon ;
Jain, Mukesh K. .
CIRCULATION RESEARCH, 2007, 100 (12) :1686-1695
[3]   A Bayesian framework for the analysis of microarray expression data: regularized t-test and statistical inferences of gene changes [J].
Baldi, P ;
Long, AD .
BIOINFORMATICS, 2001, 17 (06) :509-519
[4]  
Berk BC, 2001, ANN NY ACAD SCI, V947, P93
[5]   Inhibition of vascular permeability factor/vascular endothelial growth factor-mediated angiogenesis by the Kruppel-like factor KLF2 [J].
Bhattacharya, R ;
SenBanerjee, S ;
Lin, ZY ;
Mir, S ;
Hamik, A ;
Wang, P ;
Mukherjee, P ;
Mukhopadhyay, D ;
Jain, MK .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2005, 280 (32) :28848-28851
[6]   Key transcriptional regulators of the vasoprotective effects of shear stress [J].
Boon, R. A. ;
Horrevoets, A. J. G. .
HAMOSTASEOLOGIE, 2009, 29 (01) :39-+
[7]   KLF2 suppresses TGF-β signaling in endothelium through induction of Smad7 and inhibition of AP-1 [J].
Boon, Reinier A. ;
Fledderus, Joost O. ;
Volger, Oscar L. ;
van Wanrooij, Eva J. A. ;
Pardali, Evangelia ;
Weesie, Frank ;
Kuiper, Johan ;
Pannekoek, Hans ;
ten Dijke, Peter ;
Horrevoets, Anton J. G. .
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY, 2007, 27 (03) :532-539
[8]  
CALALB MB, 1995, MOL CELL BIOL, V15, P954
[9]   FLOW-MEDIATED ENDOTHELIAL MECHANOTRANSDUCTION [J].
DAVIES, PF .
PHYSIOLOGICAL REVIEWS, 1995, 75 (03) :519-560
[10]   Spatial relationships in early signaling events of flow-mediated endothelial mechanotransduction [J].
Davies, PF ;
Barbee, KA ;
Volin, MV ;
Robotewskyj, A ;
Chen, J ;
Joseph, L ;
Griem, ML ;
Wernick, MN ;
Jacobs, E ;
Polacek, DC ;
DePaola, N ;
Barakat, AI .
ANNUAL REVIEW OF PHYSIOLOGY, 1997, 59 :527-549