Mechanism of progesterone promoting uterine smooth muscle contraction through RhoA/ROCK signaling pathway

Xiaoli YAN; Cheng CHEN; Dan WANG; Qing CHANG

doi:10.16016/j.2097-0927.202111235

您当前的位置：

首页 >

文章列表页 >

Mechanism of progesterone promoting uterine smooth muscle contraction through RhoA/ROCK signaling pathway

Basic Medicine | 更新时间：2026-01-09

- Mechanism of progesterone promoting uterine smooth muscle contraction through RhoA/ROCK signaling pathway
- Journal of Army Medical University Vol. 44, Issue 12, Pages: 1199-1206(2022)
- 作者机构：
  
  1.400038 重庆，陆军军医大学(第三军医大学)第一附属医院妇产科
  2.401147 重庆，中国科学院大学重庆医院(重庆市人民医院)妇产科
- 作者简介：
- 基金信息：
  
  the General Program of National Natural Science Foundation of China(81771619);the General Program of National Natural Science Foundation of China(81671494)
- DOI：10.16016/j.2097-0927.202111235
  CLC： Q579.13; R329.3; R714.3
- Received：30 November 2021，
  
  Revised：2022-02-24，
  
  Published：30 June 2022
- 稿件说明：
移动端阅览
Xiaoli YAN, Cheng CHEN, Dan WANG, et al. Mechanism of progesterone promoting uterine smooth muscle contraction through RhoA/ROCK signaling pathway[J]. Journal of Army Medical University, 2022, 44(12): 1199-1206.
DOI：

Xiaoli YAN, Cheng CHEN, Dan WANG, et al. Mechanism of progesterone promoting uterine smooth muscle contraction through RhoA/ROCK signaling pathway[J]. Journal of Army Medical University, 2022, 44(12): 1199-1206. DOI： 10.16016/j.2097-0927.202111235.

摘要

目的

探讨孕酮通过RhoA/ROCK信号通路影响子宫平滑肌收缩的作用机制。

方法

收集临产与未临产人子宫平滑肌组织各5例，采用Western blot和免疫组化检测肌球蛋白轻链20磷酸化(phosphorylation of myosin light chain 20

p-MLC20)、ROCK1、ROCK2的表达；分离培养子宫平滑肌细胞并经免疫荧光技术鉴定，激光共聚焦显微镜检测细胞内游离Ca

浓度([Ca

]

i)；孕酮受体拮抗剂米非司酮及孕酮(P4)干预子宫平滑肌细胞，Western blot检测细胞中p-MLC20及ROCK1、ROCK2的表达，以及ROCK抑制剂Y-27632与孕酮干预后子宫平滑肌细胞中p-MLC20的表达。

结果

与未临产组织相比，临产子宫平滑肌组织中p-MLC20、ROCK1、ROCK2表达明显上升(

0.05)；孕酮诱导子宫平滑肌细胞后，细胞内ROCK1、ROCK2、p-MLC20水平增加(

0.05)；Y-27632与孕酮干预子宫平滑肌细胞后，细胞内p-MLC20水平下降(

0.05)。

结论

孕酮通过RhoA/ROCK信号通路调控p-MLC20水平，促进子宫平滑肌细胞收缩。

Abstract

Objective

To investigate the mechanism of progesterone affecting the contractions of uterine smooth muscle through RhoA/ROCK signaling pathway.

Methods

The tissues of uterine smooth muscle were collected from 5 cases in labor and another 5 of non-labor

respectively. The expression levels of phosphorylation of myosin light chain (p-MLC20)

ROCK1 and ROCK2 were detected by Western blotting and immunohistochemical (IHC) assay. Uterine smooth muscle cells were isolated and cultured

and then identified by im

munofluorescence assay. Laser confocal microscopy was used to measure the concentration of intracellular free Ca

([Ca

]

i) in the cells. In addition

the uterine smooth muscle cells were treated with progesterone+progesterone receptor antagonist

mifepristone

and with progesterone+ROCK inhibitor

Y-27632

respectively. Western blotting was performed to determine the expression of p-MLC20

ROCK1 and ROCK2 in the corresponding groups.

Results

As compared with the non-labor group

the expression of p-MLC20

ROCK1 and ROCK2 in the uterine smooth muscle tissues were significantly increased in the labor group (

0.05). Progesterone induced the elevation of p-MLC20

ROCK1 and ROCK2 levels in the cultured uterine smooth muscle cells (

0.05)

while after the intervention of Y-27632+progesterone

the p-MLC20 level was greatly decreased (

0.05).

Conclusion

Progesterone regulates p-MLC20 level through RhoA/ROCK signaling pathway and thus promotes the contractions of uterine smooth muscle cells.

关键词

Keywords

references

KARTERIS E, ZERVOU S, PANG Y F, et al . Progesterone signaling in human myometrium through two novel membrane G protein-coupled receptors: potential role in functional progesterone withdrawal at term[J ] . Mol Endocrinol, 2006, 20(7): 1519-1534. DOI: 10.1210/me.2005-0243.

SMITH R, MESIANO S, MCGRATH S. Hormone trajectories leading to humanbirth[J]. Regul Pept, 2002, 108(2/3): 159-164. DOI: 10.1016/s0167-0115(02)00105-2.

TONG W C, CHOI C Y, KHARCHE S, et al . A computational model of the ionic currents, Ca 2+ dynamics and action potentials underlying contraction of isolated uterine smoothmuscle[J ] . PLoS One, 2011, 6(4): e18685. DOI: 10.1371/journal.pone.0018685..

FITZGERALD A C, PEYTON C, DONG J, et al . Bisphenol A and related alkylphenols exert nongenomic estrogenic actions through a G protein-coupled estrogen receptor 1 (Gper)/epidermal growth factor receptor (Egfr) pathway to inhibit meiotic maturation of zebrafish oocytes[J ] . Biol Reprod, 2015, 93(6): 135, 1-11. DOI: 10.1095/biolreprod.115.132316.

THOMAS P, TUBBS C, GARRY V F. Progestin functions in vertebrate gametes mediated by membrane progestin receptors (mPRs): identification of mPRalpha on human sperm and its association with sperm motility[J]. Steroids, 2009, 74(7): 614-621. DOI: 10.1016/j.steroids.2008.10.020.

BAI L Y, KEE H J, CHOI S Y, et al . HDAC5 inhibition reduces angiotensin Ⅱ-induced vascular contraction, hypertrophy, and oxidative stress in a mouse model[J ] . Biomed Pharmacother, 2021, 134: 111162. DOI: 10.1016/j.biopha.2020.111162.

LIU Z W, KHALIL R A. Evolving mechanisms of vascular smooth muscle contraction highlight key targets in vascular disease[J]. Biochem Pharmacol, 2018, 153: 91-122. DOI: 10.1016/j.bcp.2018.02.012.

SWENARCHUK L E. Nerve, muscle, and synaptogenesis[J]. Cells, 2019, 8(11): 1448. DOI: 10.3390/cells8111448.

LIU L, OZA S, HOGAN D, et al . Global, regional, and national causes of under-5 mortality in 2000-15: an updated systematic analysis with implications for the Sustainable Development Goals[J ] . Lancet, 2016, 388(10063): 3027-3035. DOI: 10.1016/S0140-6736(16)31593-8.

BLENCOWE H, COUSENS S, OESTERGAARD M Z, et al . National, regional, and worldwide estimates of preterm birth rates in the year 2010 with time trends since 1990 for selected countries: a systematic analysis and implications[J ] . Lancet, 2012, 379(9832): 2162-2172. DOI: 10.1016/S0140-6736(12)60820-4.

SHATTOCK M J, OTTOLIA M, BERS D M, et al . Na + /Ca 2+ exchange and Na + /K + -ATPase in the heart[J ] . J Physiol, 2015, 593(6): 1361-1382. DOI: 10.1113/jphysiol.2014.282319..

EISNER D A, CALDWELL J L, KISTAMÁS K, et al . Calcium and excitation-contraction coupling in the heart[J ] . Circ Res, 2017, 121(2): 181-195. DOI: 10.1161/CIRCRESAHA.117.310230.

LU P, CHEN J, ZHANG C H, et al . Oscillating calcium signals in smooth muscle cells underlie the persistent basal tone of internal anal sphincter[J ] . J Cel l Physiol, 2021, 236(8): 5937-5952. DOI: 10.1002/jcp.30279.

JO M H, KIM B C, SUNGK, et al . Molecular nanomechanical mapping of histamine-induced smooth muscle cell contraction and shortening[J ] . ACS Nano, 2021. DOI: 10.1021/acsnano.1c01782.[Onlineaheadofprint ] .

SANDERS K M, KOH S D, RO S, et al . Regulation of gastrointestinal motility: insights from smooth muscle biology[J ] . Nat Rev Gastroenterol Hepatol, 2012, 9(11): 633-645. DOI: 10.1038/nrgastro.2012.168.

ACKERMAN W E 4th, BUHIMSCHI I A, BRUBAKER D, et al . Integrated microRNA and mRNA network analysis of the humanmyometrial transcriptome in the transition from quiescence to labor[J ] . Biol Reprod, 2018, 98(6): 834-845. DOI: 10.1093/biolre/ioy040.

SUELDO C, LIU X F, PELUSO J J. Progestin and AdipoQ receptor 7, progesterone membrane receptor component 1 (PGRMC1), and PGRMC2 and their role in regulating progesterone's ability to suppress human granulosa/luteal cells from entering into the cell cycle[J]. Biol Reprod, 2015, 93(3): 63. DOI: 10.1095/biolreprod.115.131508.

SEMIZ A T, TEKER A B, YAPAR K, et al . Hydrogen sulfide dilates the isolated retinal artery mainly via the activation of myosin phosphatase[J ] . LifeSci, 2020, 255: 117834. DOI: 10.1016/j.lfs.2020.117834..

SUN J, TAO T, ZHAO W, et al . CPI-17-mediated contraction of vascular smooth muscle is essential for the development of hypertension in obesemice[J ] . J Genet Genomics, 2019, 46(3): 109-118. DOI: 10.1016/j.jgg.2019.02.005.

SHIMOKAWA H, SUNAMURA S, SATOH K. RhoA/rho-kinase in the cardiovascular system[J]. Circ Res, 2016, 118(2): 352-366. DOI: 10.1161/CIRCRESAHA.115.306532.

高洁, 丁依玲. 子宫平滑肌组织中RhoA及Rho激酶的表达与分娩发动的关系[J]. 中华妇产科杂志, 2009, 44(5): 345-349. DOI: 10.3760/cma.j.issn.0529-567x.2009.05.007.

GAO J, DING Y L. Correlation between expression of RhoA and Rho kinase in uterine smooth muscle and the onset of labor[J]. Chin J Obstet Gynecol, 2009, 44(5): 345-349. DOI:10.3760/cma.j.issn.0529-567x.2009.05.007.

Views

下载量

CSCD

Alert me when the article has been cited

提交

Tools

Publicity Resources

Deltex-1 overexpression suppresses proliferation and promotes differentiation of bone marrow mesenchymal stem cells into smooth muscle cells in vitro

Peroxisome proliferators-activated receptor-gamma agonist inhibits angiotensin Ⅱ-induced phenotypic switching of vascular smooth muscle cells

Bone marrow-derived mesenchymal stem cells improve acontractile detrusor in rat model

TGF-β₁ promotes endothelial cells adhesion to smooth muscle cells

Construction of eukaryotic vector expressing Jagged1 gene and its effect on prolife-ration and apoptosis of vascular smooth muscle cells

Related Author

Huicheng XU

Lubin LIU

Yanzhou WANG

Ying WANG

陈康宁

胡晓露

高飞

周占松

Related Institution

Chongqing Maternal and Child Healthcare Hospital

Department of Obstetrics and Gynecology, First Affiliated Hospital, Army Medical Universtity (Third Military Medical University)

⁰