Thyroid hormone induces artery smooth muscle cell proliferation: discovery of a new TRalpha1-Nox1 pathway.
Thyroid hormone induces artery smooth muscle cell proliferation: discovery of a new TRalpha1-Nox1 pathway.
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DOI：
10.1111/j.1582-4934.2008.00489.x
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发表时间：
2010-01
影响因子：
5.3
通讯作者：
Sun Z
中科院分区：
文献类型：
--
作者：
Wang X;Sun Z
甲状腺激素（T3）可以刺激蛋白质合成和细胞生长。NOX1是一种促有丝分裂氧化酶。本研究的目的是验证一个新的假设，即T3通过上调NOX1诱导动脉平滑肌细胞增殖。应用免疫荧光共聚焦显微镜观察大鼠主动脉平滑肌细胞（RASM）中NOX1和TR α 1的亚细胞定位。光学切片显示TR α 1和NOX 1共定位于细胞核周围。T3可促进RASM细胞增殖，表现为胞质分裂细胞数、增殖细胞核抗原（PCNA）和平滑肌α-肌动蛋白（SM α-actin）明显增加。T3分别在转录（mRNA）和翻译（蛋白质）水平上增加了NOX1的表达，如通过RT-PCR和Western blot所评估的。T3还基于2 '，7'-二氯二氢荧光素（H2DCF）氧化成荧光2'，7'-二氯荧光素（DCF）而显著增加细胞内ROS产生。RNAi沉默TR α 1或NOX 1可抑制T3诱导的RASM细胞内ROS的产生以及PCNA和SM α-actin的表达，表明TR α 1和NOX 1介导了T3诱导的RASM细胞增殖。值得注意的是，RNA干扰沉默TR α 1阻断了T3诱导的NOX 1表达的增加，而NOX 1的沉默不影响TR α 1的表达，揭示了一种新的途径，即T3-TR α 1-NOX 1-细胞增殖。TR α 1和NOX 1共定位于细胞核周围。T3通过TR α 1依赖性上调NOX1的表达诱导RASM细胞增殖。
Thyroid hormone (T3) can stimulate protein synthesis and cell growth. NOX1 is a mitogenic oxidase. The aim of this study was to test a novel hypothesis that T3 induces artery smooth muscle cell proliferation by up-regulating NOX1. Immunofluoresence confocal microscopy was used to visualize the sub-cellular localization of NOX1 and TRα1 in rat aorta smooth muscle (RASM) cells. Optical sectioning showed that TRα1 and NOX1 co-localized around the nucleus. T3 promoted RASM cell proliferation as determined by the fact that T3 significantly increased the number of cytokinesis cells, proliferating cellular nuclear antigen (PCNA) and smooth muscle α-actin (SM α-actin). T3 increased NOX1 expression at both the transcription (mRNA) and translation (protein) levels as evaluated by RT-PCR and Western blot, respectively. T3 also significantly increased the intracellular ROS production based on the oxidation of 2’,7’-dichlorodihydrofluoresein (H2DCF) to a fluorescent 2’,7’-dichlorofluoresein (DCF). RNAi silence of TRα1 or NOX1 abolished T3-induced intracellular ROS generation and PCNA and SM α-actin expression, indicating that TRα1 and NOX1 mediated T3-induced RASM cell proliferation. Notably, RNAi silence of TRα1 blocked the T3-induced increase in NOX1 expression, whereas silence of NOX1 did not affect TRα1 expression, disclosing a new pathway, i.e. T3-TRα1-NOX1-cell proliferation. TRα1 and NOX1 co-localized around the nucleus. T3 induced RASM cell proliferation by up-regulating NOX1 in a TRα1-dependent manner.
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影响因子：
64.8
作者：
KOENIG, RJ;LAZAR, MA;MOORE, DD
通讯作者：
MOORE, DD
影响因子：
64.8
作者：
BRAVO, R;FRANK, R;MACDONALDBRAVO, H
通讯作者：
MACDONALDBRAVO, H
影响因子：
5.9
作者：
DILLMANN, WH
通讯作者：
DILLMANN, WH
影响因子：
5.3
作者：
Kasahara, T;Tsunekawa, K;Murakami, M
通讯作者：
Murakami, M
影响因子：
20.1
作者：
GRIENDLING, KK;MINIERI, CA;ALEXANDER, RW
通讯作者：
ALEXANDER, RW