Tyrosine-kinase dependent TGF-beta and extracellular matrix expression by mechanical stretch in vascular smooth muscle cells.
Tyrosine-kinase dependent TGF-beta and extracellular matrix expression by mechanical stretch in vascular smooth muscle cells.
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血管平滑肌细胞中机械拉伸导致酪氨酸激酶依赖性 TGF-β 和细胞外基质表达。
DOI：
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发表时间：
2000
影响因子：
5.4
通讯作者：
Kiyoshi Kurokawa
中科院分区：
文献类型：
--
作者：
Nobuhiko Joki;Shinya Kaname;Masao Hirakata;Y. Hori;Tetsu Yamaguchi;Toshiro Fujita;Tetsuo Katoh;Kiyoshi Kurokawa
血管肥大以血管平滑肌细胞（VSMC）的增生和细胞外基质（ECM）的积累为特征，是慢性高血压暴露后血管的主要病理改变。血压传递到动脉壁，并被机械应力平衡，导致向周向的VSMC拉伸，这可能在血管肥大的发病机制中起一定作用。因此，本研究旨在探讨机械拉伸对ECM成分和转化生长因子- β (tgf - β)表达的影响，并探讨tgf - β在培养大鼠VSMC中诱导的信号转导机制。tgf - β是ECM产生的有效刺激物。VSMC进行循环拉伸，以每分钟60次的速率提供20%的最大伸长率，长达24小时。机械拉伸以时间和长度依赖的方式刺激tgf - β 1 mRNA的表达。事实上，拉伸后tgf - β蛋白在培养基中的分泌量增加。拉伸也刺激了ECM成分、I型和IV型胶原和纤维连接蛋白的mRNA表达，而加入抗tgf - β的中和抗体则在很大程度上抑制了这种表达。酪氨酸激酶抑制剂染料木素和herbimycin A通过拉伸阻断tgf - β 1和I型胶原的诱导，而蛋白激酶C抑制剂、钙通道阻滞剂尼群地平和钆或从培养基中去除Ca没有效果。这些结果表明，拉伸诱导的酪氨酸激酶介导的TGF-8的自分泌/旁分泌产生可能在高血压相关血管重构的进展中发挥关键作用。
Vascular hypertrophy, which is characterized by proliferation of vascular smooth muscle cells (VSMC) and accumulation of extracellular matrix (ECM), is a major pathological change in blood vessels after chronic exposure to hypertension. Blood pressure is transmitted to the arterial walls and counterbalanced by mechanical stress, leading to stretching of circumferentially oriented VSMC, which may play some role in the pathogenesis of vascular hypertrophy. The present study was designed, therefore, to investigate the effect of mechanical stretch on the expression of ECM components and transforming growth factor-beta (TGF-beta), a potent stimulator for ECM production, and to examine the signal transduction mechanisms of the induction of TGF-beta in cultured rat VSMC. VSMC were subjected to cyclic stretch to provide a maximal elongation of 20% at a rate of 60 cycles per minute for up to 24 h. Mechanical stretch stimulated TGF-beta1 mRNA expression in a time- and elongation-dependent manner. Indeed, the secretion of TGF-beta proteins into the culture media was increased after stretch. Stretch also stimulated mRNA expression of the ECM components, type I and type IV collagen, and fibronectin, which was largely inhibited by addition of neutralizing antibody against TGF-beta. The tyrosine kinase inhibitors genistein and herbimycin A blocked the induction of TGF-beta1 and type I collagen by stretch, while protein kinase C inhibitors, the calcium channel blockers nitrendipine and gadolinium, or Ca removal from the media had no effect. These results suggest that stretch-induced, tyrosine kinase-mediated autocrine/paracrine production of TGF-8 may play a critical role in the progression of vascular remodeling associated with high blood pressure.
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DOI：
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发表时间：
1986-03
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
R. Ignotz;J. Massagué
通讯作者：
R. Ignotz;J. Massagué
大鼠肾小球系膜细胞重复拉伸和松弛循环激活 S6 激酶。
DOI：
--
发表时间：
1992
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Homma,T;Akai,Y;Burns,KD;Harris,RC
通讯作者：
Harris,RC
影响因子：
20.1
作者：
Reusch, P;Wagdy, H;Ives, HE
通讯作者：
Ives, HE
正常血脂和高血脂血清对主动脉平滑肌细胞循环拉伸生物合成反应的影响。
DOI：
10.1161/01.atv.9.4.446
发表时间：
1989
期刊：
Arteriosclerosis (Dallas, Tex.)
影响因子：
--
作者：
Grande,JP;Glagov,S;Bates,SR;Horwitz,AL;Mathews,MB
通讯作者：
Mathews,MB
在重复机械拉伸过程中平滑肌细胞增强胶原蛋白的产生。
DOI：
10.1001/archsurg.1988.01400340059010
发表时间：
1988
期刊：
Archives of surgery (Chicago, Ill. : 1960)
影响因子：
--
作者：
Sumpio,BE;Banes,AJ;Link,WG;JohnsonJr,G
通讯作者：
JohnsonJr,G