Modulation of RhoA—Rho kinase‐mediated Ca2+ sensitization of rabbit myometrium during pregnancy — role of Rnd3
Modulation of RhoA—Rho kinase‐mediated Ca2+ sensitization of rabbit myometrium during pregnancy — role of Rnd3
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妊娠期间 RhoA——Rho 激酶介导的兔子宫肌层 Ca2+ 敏化的调节——Rnd3 的作用
DOI：
10.1111/j.1469-7793.2003.00403.x
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发表时间：
2003
期刊：
影响因子：
--
通讯作者：
P. Pacaud
中科院分区：
文献类型：
--
作者：
C. Cario‐Toumaniantz;G. Reillaudoux;V. Sauzeau;F. Heutte;Vaillant;M. Finet;Pierre Chardin;G. Loirand;P. Pacaud
在怀孕期间，子宫经历了主要的功能和结构重塑。众所周知，在怀孕的大部分时间里，子宫肌层通常保持相对静止，但在分娩时能够产生强大的收缩。然而，在怀孕期间调节子宫肌收缩的细胞内分子事件仍然知之甚少。我们使用cDNA阵列技术对未怀孕和怀孕中期（15天）家兔的肌层样本进行差异基因表达筛选。在差异表达基因中，Rho家族的法酰化小G蛋白Rnd3在妊娠中期被发现上调（3.6倍）。妊娠中期子宫肌层Rnd3表达增加3.4倍，证实了Rnd3在蛋白水平上的上调。β - escin渗透平滑肌条的收缩特性测量显示，Rnd3的上调与妊娠中期RhoA - Rho激酶介导的Ca2+敏化的抑制相关。用法尼基转移酶抑制剂马霉素A （10 μM）处理妊娠中期肌层肌肉条，可恢复RhoA - Rho激酶依赖性Ca2+敏化。在妊娠后期（31天），RhoA和Rho激酶表达上调与Rho激酶抑制剂Y‐27632 （10 μM）抑制收缩蛋白Ca2+敏感性的增加有关。因此，这些数据证明了RhoA - Rho激酶介导的Ca2+敏化在妊娠过程中的时间依赖性调节。这一机制在妊娠中期被抑制，随后在妊娠中期被激活，这与Rnd3、RhoA和Rho激酶表达的协同调节有关。因此，RhoA - Rho激酶信号通路及其调控因子可能代表了开发新的早产治疗方法的潜在靶点。
During pregnancy, the uterus undergoes major functional and structural remodelling. It is well known that during the major part of pregnancy, the myometrium normally remains relatively quiescent but is able to generate powerful contractions at the time of parturition. However, the intracellular molecular events regulating myometrial contractility during pregnancy still remain poorly understood. We applied differential gene expression screening using cDNA array technology to probe myometrium samples from non‐pregnant and mid‐pregnant (15 days) rabbits. Among the differentially expressed genes, the farnesylated small G‐protein of the Rho family, Rnd3, was found to be upregulated (3.6‐fold) at mid‐pregnancy. Upregulation of Rnd3 was confirmed at the protein level by a 3.4‐fold increase in Rnd3 expression in mid‐pregnant myometrium. Measurements of contractile properties of β‐escin permeabilized smooth muscle strips revealed that the upregulation of Rnd3 correlated with an inhibition of RhoA‐Rho kinase‐mediated Ca2+ sensitization at mid‐pregnancy. Treatment of muscle strips from mid‐pregnant myometrium with the farnesyl‐transferase inhibitor manumycin A (10 μM) led to the recovery of RhoA‐Rho kinase‐dependent Ca2+ sensitization. At late pregnancy (31 days), upregulation of RhoA and Rho kinase expression was associated with an increase in Ca2+ sensitivity of contractile proteins that was inhibited by the Rho kinase inhibitor Y‐27632 (10 μM). These data thus demonstrate the time‐dependent regulation of the RhoA‐Rho kinase‐mediated Ca2+ sensitization during the course of pregnancy. The depression of this mechanism at mid‐pregnancy followed by its constitutive activation near term is associated with a co‐ordinated modulation of Rnd3, RhoA and Rho kinase expression. The RhoA‐Rho kinase signalling pathway and its regulators might thus represent potential targets for the development of new treatments for pre‐term labour.
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影响因子：
3.7
作者：
Taggart, MJ;Lee, YH;Morgan, KG
通讯作者：
Morgan, KG
DOI：
10.1073/pnas.93.3.1340
发表时间：
1996-02-06
影响因子：
11.1
作者：
Gong, MC;Iizuka, K;Somlyo, AP
通讯作者：
Somlyo, AP
DOI：
10.1073/pnas.90.6.2281
发表时间：
1993-03-15
影响因子：
11.1
作者：
HARA, M;AKASAKA, K;TAMANOI, F
通讯作者：
TAMANOI, F
影响因子：
--
作者：
INOUE, Y;SPERELAKIS, N
通讯作者：
SPERELAKIS, N