RhoA and Rho-kinase inhibitors modulate cervical resistance

The possible role of RhoA/Rho-kinase signalling pathway in cervical ripening and contractility

Dóra Domokos, Eszter Ducza, R. Gáspár

Research output: Contribution to journalArticle

Abstract

Improper cervical function may lead premature or late-term birth. The RhoA/Rho-kinase (ROCK) signalling pathway takes part in cellular functions including smooth muscle contraction. No information is available about the cervical expression of the RhoA/ROCK system during pregnancy. Our aim was to detect the mRNA and protein expression of ROCK enzymes in rat cervices and to evaluate the effects of RhoA/ROCK inhibitors on cervical resistance. The mRNA and protein expressions of RhoA, ROCK I and II were measured in non-pregnant, pregnant and postpartum rat cervices and during parturition by Real-time qPCR and Western blot. The cervical resistance modifying effects of RhoA (simvastatin) and ROCK (fasudil, Y-27632) (10−6M) were investigated in tissue bath experiments. RhoA mRNA was increased on post-partum day 3, while the RhoA protein expression was decreased near and during parturition. ROCK I mRNA and protein expressions were fluctuating with a decrease in protein expression during parturition. ROCK II mRNA and protein expressions were sharply reduced during parturition. Simvastatin increased the cervical resistance on pregnancy days 20 and 22 while Y-27632 and fasudil reduced the resistance on pregnancy days 20. The decrease in RhoA/ROCK expression near parturition may take part in cervical ripening, especially in the final processes leading to delivery. ROCK inhibitors might be potential drug candidates to treat insufficient cervical ripening late-term pregnancies. The effect of simvastatin possibly due to its unique smooth muscle contracting activity in pregnant cervix. Compounds with simvastatin-like action might be new drug candidates for preterm cervical ripening.

Original languageEnglish
Pages (from-to)27-33
Number of pages7
JournalEuropean Journal of Pharmacology
Volume843
DOIs
Publication statusPublished - Jan 15 2019

Fingerprint

Cervical Ripening
rho-Associated Kinases
Simvastatin
Parturition
rhoA GTP-Binding Protein
Messenger RNA
Cervix Uteri
Pregnancy
Smooth Muscle
Proteins
Term Birth
Muscle Contraction
Baths
Pharmaceutical Preparations
Postpartum Period
Western Blotting
Enzymes

Keywords

  • Cervical ripening
  • Fasudil
  • Pregnancy
  • Pregnancy
  • RhoA/ROCK pathway
  • Simvastatin

ASJC Scopus subject areas

  • Pharmacology

Cite this

@article{e846b5fa37f1414d87db6a5e037bc467,
title = "RhoA and Rho-kinase inhibitors modulate cervical resistance: The possible role of RhoA/Rho-kinase signalling pathway in cervical ripening and contractility",
abstract = "Improper cervical function may lead premature or late-term birth. The RhoA/Rho-kinase (ROCK) signalling pathway takes part in cellular functions including smooth muscle contraction. No information is available about the cervical expression of the RhoA/ROCK system during pregnancy. Our aim was to detect the mRNA and protein expression of ROCK enzymes in rat cervices and to evaluate the effects of RhoA/ROCK inhibitors on cervical resistance. The mRNA and protein expressions of RhoA, ROCK I and II were measured in non-pregnant, pregnant and postpartum rat cervices and during parturition by Real-time qPCR and Western blot. The cervical resistance modifying effects of RhoA (simvastatin) and ROCK (fasudil, Y-27632) (10−6M) were investigated in tissue bath experiments. RhoA mRNA was increased on post-partum day 3, while the RhoA protein expression was decreased near and during parturition. ROCK I mRNA and protein expressions were fluctuating with a decrease in protein expression during parturition. ROCK II mRNA and protein expressions were sharply reduced during parturition. Simvastatin increased the cervical resistance on pregnancy days 20 and 22 while Y-27632 and fasudil reduced the resistance on pregnancy days 20. The decrease in RhoA/ROCK expression near parturition may take part in cervical ripening, especially in the final processes leading to delivery. ROCK inhibitors might be potential drug candidates to treat insufficient cervical ripening late-term pregnancies. The effect of simvastatin possibly due to its unique smooth muscle contracting activity in pregnant cervix. Compounds with simvastatin-like action might be new drug candidates for preterm cervical ripening.",
keywords = "Cervical ripening, Fasudil, Pregnancy, Pregnancy, RhoA/ROCK pathway, Simvastatin",
author = "D{\'o}ra Domokos and Eszter Ducza and R. G{\'a}sp{\'a}r",
year = "2019",
month = "1",
day = "15",
doi = "10.1016/j.ejphar.2018.11.017",
language = "English",
volume = "843",
pages = "27--33",
journal = "European Journal of Pharmacology",
issn = "0014-2999",
publisher = "Elsevier",

}

TY - JOUR

T1 - RhoA and Rho-kinase inhibitors modulate cervical resistance

T2 - The possible role of RhoA/Rho-kinase signalling pathway in cervical ripening and contractility

AU - Domokos, Dóra

AU - Ducza, Eszter

AU - Gáspár, R.

PY - 2019/1/15

Y1 - 2019/1/15

N2 - Improper cervical function may lead premature or late-term birth. The RhoA/Rho-kinase (ROCK) signalling pathway takes part in cellular functions including smooth muscle contraction. No information is available about the cervical expression of the RhoA/ROCK system during pregnancy. Our aim was to detect the mRNA and protein expression of ROCK enzymes in rat cervices and to evaluate the effects of RhoA/ROCK inhibitors on cervical resistance. The mRNA and protein expressions of RhoA, ROCK I and II were measured in non-pregnant, pregnant and postpartum rat cervices and during parturition by Real-time qPCR and Western blot. The cervical resistance modifying effects of RhoA (simvastatin) and ROCK (fasudil, Y-27632) (10−6M) were investigated in tissue bath experiments. RhoA mRNA was increased on post-partum day 3, while the RhoA protein expression was decreased near and during parturition. ROCK I mRNA and protein expressions were fluctuating with a decrease in protein expression during parturition. ROCK II mRNA and protein expressions were sharply reduced during parturition. Simvastatin increased the cervical resistance on pregnancy days 20 and 22 while Y-27632 and fasudil reduced the resistance on pregnancy days 20. The decrease in RhoA/ROCK expression near parturition may take part in cervical ripening, especially in the final processes leading to delivery. ROCK inhibitors might be potential drug candidates to treat insufficient cervical ripening late-term pregnancies. The effect of simvastatin possibly due to its unique smooth muscle contracting activity in pregnant cervix. Compounds with simvastatin-like action might be new drug candidates for preterm cervical ripening.

AB - Improper cervical function may lead premature or late-term birth. The RhoA/Rho-kinase (ROCK) signalling pathway takes part in cellular functions including smooth muscle contraction. No information is available about the cervical expression of the RhoA/ROCK system during pregnancy. Our aim was to detect the mRNA and protein expression of ROCK enzymes in rat cervices and to evaluate the effects of RhoA/ROCK inhibitors on cervical resistance. The mRNA and protein expressions of RhoA, ROCK I and II were measured in non-pregnant, pregnant and postpartum rat cervices and during parturition by Real-time qPCR and Western blot. The cervical resistance modifying effects of RhoA (simvastatin) and ROCK (fasudil, Y-27632) (10−6M) were investigated in tissue bath experiments. RhoA mRNA was increased on post-partum day 3, while the RhoA protein expression was decreased near and during parturition. ROCK I mRNA and protein expressions were fluctuating with a decrease in protein expression during parturition. ROCK II mRNA and protein expressions were sharply reduced during parturition. Simvastatin increased the cervical resistance on pregnancy days 20 and 22 while Y-27632 and fasudil reduced the resistance on pregnancy days 20. The decrease in RhoA/ROCK expression near parturition may take part in cervical ripening, especially in the final processes leading to delivery. ROCK inhibitors might be potential drug candidates to treat insufficient cervical ripening late-term pregnancies. The effect of simvastatin possibly due to its unique smooth muscle contracting activity in pregnant cervix. Compounds with simvastatin-like action might be new drug candidates for preterm cervical ripening.

KW - Cervical ripening

KW - Fasudil

KW - Pregnancy

KW - Pregnancy

KW - RhoA/ROCK pathway

KW - Simvastatin

UR - http://www.scopus.com/inward/record.url?scp=85056772946&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85056772946&partnerID=8YFLogxK

U2 - 10.1016/j.ejphar.2018.11.017

DO - 10.1016/j.ejphar.2018.11.017

M3 - Article

VL - 843

SP - 27

EP - 33

JO - European Journal of Pharmacology

JF - European Journal of Pharmacology

SN - 0014-2999

ER -