Abnormal Activation of RhoA/ROCK-I Signaling in Junctional Zone Smooth Muscle Cells of Patients With Adenomyosis
Abnormal Activation of RhoA/ROCK-I Signaling in Junctional Zone Smooth Muscle Cells of Patients With Adenomyosis
复制标题
子宫腺肌病患者交界区平滑肌细胞 RhoA/ROCK-I 信号异常激活
DOI：
10.1177/1933719115602764
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发表时间：
2016-03-01
影响因子：
2.9
通讯作者：
Sun, F. Q.
中科院分区：
文献类型：
--
作者：
Wang, S.;Duan, H.;Sun, F. Q.
子宫腺肌病是一种常见的雌激素依赖性妇科疾病，病因不明。RhoA/Rho激酶（ROCK）信号通路参与多种细胞功能，包括迁移、增殖和平滑肌收缩。在这里，我们研究了这一途径的潜在作用，在交界区（JZ）收缩的妇女和没有ADS。我们证明，在正常的JZ，RhoA和ROCK-I信使RNA（mRNA）和蛋白质的表达显着高于在月经周期的增殖期比分泌期。RhoA和ROCK-I在ADS女性JZ中的表达显著高于对照女性，并且在整个月经周期中没有显着差异。用0、1、10或100 nmol/L雌激素处理JZ平滑肌细胞（JZSMCs）24 h后，RhoA、ROCK-I和肌球蛋白轻链（MLC）磷酸化（p-MLC）的表达呈剂量依赖性增加。与其对p-MLC的影响平行，JZSMCs中雌激素介导的剂量依赖性收缩反应。雌激素介导的收缩在ADS组显着高于对照组，也没有显示出在整个月经周期的显着差异。这些作用在ICI 182780或Y27632的存在下被抑制，支持雌激素受体依赖性和RhoA激活依赖性机制。我们的研究结果表明，RhoA和ROCK-I水平增加，ADS患者的周期变化丢失。雌激素可能通过增强RhoA/ROCK-I信号通路影响子宫JZ收缩。
Adenomyosis (ADS) is a common estrogen-dependent gynecological disease with unknown etiology. The RhoA/Rho-kinase (ROCK) signaling pathway is involved in various cellular functions, including migration, proliferation, and smooth muscle contraction. Here we examined the potential role of this pathway in junctional zone (JZ) contraction in women with and without ADS. We demonstrated that in the normal JZ, RhoA and ROCK-I messenger RNA (mRNA) and protein expression was significantly higher in the proliferative phase of the menstrual cycle than in the secretory phase. Expression of RhoA and ROCK-I in the JZ from women with ADS was significantly higher than in the control women and showed no significant differences across the menstrual cycle. Treatment of JZ smooth muscle cells (JZSMCs) with estrogen at 0, 1, 10, or 100 nmol/L for 24 hours resulted in increased expression of RhoA, ROCK-I, and myosin light-chain (MLC) phosphorylation (p-MLC) in a dose-dependent manner. In parallel to its effects on p-MLC, estrogen-mediated, dose-dependent contraction responses in JZSMCs. Estrogen-mediated contraction in the ADS group was significantly higher than in the controls and also showed no significant differences across the menstrual cycle. These effects were suppressed in the presence of ICI 182780 or Y27632, supporting an estrogen receptor-dependent and RhoA activation-dependent mechanism. Our results indicate that the level of RhoA and ROCK-I increases in patients with ADS and the cyclic change is lost. Estrogen may affect uterine JZ contraction of ADS by enhancing RhoA/ ROCK-I signaling.