Molecular Mechanism of Fibronectin Gene Activation by Cyclic Stretch in Vascular Smooth Muscle Cells*
Molecular Mechanism of Fibronectin Gene Activation by Cyclic Stretch in Vascular Smooth Muscle Cells*
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血管平滑肌细胞循环拉伸激活纤连蛋白基因的分子机制*
DOI：
10.1074/jbc.m004421200
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发表时间：
2000
期刊：
影响因子：
--
通讯作者：
S. Umemura
中科院分区：
文献类型：
--
作者：
Kouichi Tamura;Y. Chen;M. Lopez;L. Daviet;N. Tamura;T. Ishigami;M. Akishita;I. Takasaki;Y. Tokita;R. Pratt;M. Horiuchi;V. Dzau;S. Umemura
纤维连接蛋白在血管重塑中发挥重要作用。机械刺激和局部产生的血管活性剂之间的功能相互作用被认为是血管重塑的关键。我们研究了机械拉伸对血管平滑肌细胞中纤连蛋白基因表达的影响，以及血管紧张素II在响应拉伸的纤连蛋白基因调节中的作用。周期性拉伸诱导血管纤连蛋白mRNA水平的增加，抑制放线菌素D和CV11974，血管紧张素II 1型受体拮抗剂;放线菌酮和PD 123319，血管紧张素II 2型受体拮抗剂，不影响诱导。在转染实验中，纤连蛋白启动子活性的刺激拉伸和抑制CV11974，但不是由PD 123319。DNA-蛋白质结合实验表明，环状拉伸增强了细胞核与AP-1位点的结合，而AP-1位点的定点突变显著降低了环状拉伸介导的纤连蛋白启动子的激活。此外，反义c-jun寡核苷酸降低牵张诱导的纤连蛋白启动子活性和mRNA表达的刺激。这些结果表明，周期性拉伸刺激血管纤连蛋白基因的表达，主要是通过激活AP-1通过血管紧张素II 1型受体。
Fibronectin plays an important role in vascular remodeling. A functional interaction between mechanical stimuli and locally produced vasoactive agents is suggested to be crucial for vascular remodeling. We examined the effect of mechanical stretch on fibronectin gene expression in vascular smooth muscle cells and the role of vascular angiotensin II in the regulation of the fibronectin gene in response to stretch. Cyclic stretch induced an increase in vascular fibronectin mRNA levels that was inhibited by actinomycin D and CV11974, an angiotensin II type 1 receptor antagonist; cycloheximide and PD123319, an angiotensin II type 2 receptor antagonist, did not affect the induction. In transfection experiments, fibronectin promoter activity was stimulated by stretch and inhibited by CV11974 but not by PD123319. DNA-protein binding experiments revealed that cyclic stretch enhanced nuclear binding to the AP-1 site, which was partially supershifted by antibody to c-Jun. Site-directed mutation of the AP-1 site significantly decreased the cyclic stretch-mediated activation of fibronectin promoter. Furthermore, antisense c-jun oligonucleotides decreased the stretch-induced stimulation of the fibronectin promoter activity and the mRNA expression. These results suggest that cyclic stretch stimulates vascular fibronectin gene expression mainly via the activation of AP-1 through the angiotensin II type 1 receptor.
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影响因子：
4
作者：
A. Banes;J. Gilbert;D. Taylor;O. Monbureau
通讯作者：
A. Banes;J. Gilbert;D. Taylor;O. Monbureau
高血压对大鼠主动脉纤连蛋白表达的影响。
DOI：
--
发表时间：
1990
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Takasaki,I;Chobanian,AV;Sarzani,R;Brecher,P
通讯作者：
Brecher,P
影响因子：
15.9
作者：
KAGAMI, S;BORDER, WA;NOBLE, NA
通讯作者：
NOBLE, NA
影响因子：
2.2
作者：
GREEN, LM;READE, JL;WARE, CF
通讯作者：
WARE, CF
DOI：
10.1016/s0021-9258(17)37619-6
发表时间：
1994-02
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
A. Lokuta;C. Cooper;S. Gaa;H. Wang;T. B. Rogers
通讯作者：
A. Lokuta;C. Cooper;S. Gaa;H. Wang;T. B. Rogers