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Rho-Kinase Inhibition of Active Force and Passive Tension in Airway Smooth Muscle: A Strategy for Treating Airway Hyperresponsiveness in Asthma.

作者信息

Yasuda Yuto, Wang Lu, Chitano Pasquale, Seow Chun Y

机构信息

Centre for Heart Lung Innovation, St. Paul's Hospital, Providence Health Care, University of British Columbia, Vancouver, BC V6Z 1Y6, Canada.

Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC V6Z 1Y6, Canada.

出版信息

Biology (Basel). 2024 Feb 11;13(2):115. doi: 10.3390/biology13020115.


DOI:10.3390/biology13020115
PMID:38392332
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10886476/
Abstract

Rho-kinase inhibitors have been identified as a class of potential drugs for treating asthma because of their ability to reduce airway inflammation and active force in airway smooth muscle (ASM). Past research has revealed that, besides the effect on the ASM's force generation, rho-kinase (ROCK) also regulates actin filament formation and filament network architecture and integrity, thus affecting ASM's cytoskeletal stiffness. The present review is not a comprehensive examination of the roles played by ROCK in regulating ASM function but is specifically focused on passive tension, which is partially determined by the cytoskeletal stiffness of ASM. Understanding the molecular basis for maintaining active force and passive tension in ASM by ROCK will allow us to determine the suitability of ROCK inhibitors and its downstream enzymes as a class of drugs in treating airway hyperresponsiveness seen in asthma. Because clinical trials using ROCK inhibitors in the treatment of asthma have yet to be conducted, the present review focuses on the in vitro effects of ROCK inhibitors on ASM's mechanical properties which include active force generation, relaxation, and passive stiffness. The review provides justification for future clinical trials in the treatment of asthma using ROCK inhibitors alone and in combination with other pharmacological and mechanical interventions.

摘要
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/125c/10886476/0d9f2e70a13a/biology-13-00115-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/125c/10886476/0d9f2e70a13a/biology-13-00115-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/125c/10886476/0d9f2e70a13a/biology-13-00115-g001.jpg

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Rho-Kinase Inhibition of Active Force and Passive Tension in Airway Smooth Muscle: A Strategy for Treating Airway Hyperresponsiveness in Asthma.

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引用本文的文献

[1]
Targeting cytoskeletal biomechanics to modulate airway smooth muscle contraction in asthma.

J Biol Chem. 2025-1

[2]
Bronchomotor tone imbalance evokes airway hyperresponsiveness.

Expert Rev Respir Med. 2024-11

[3]
Serum Response Factor Overexpression, a Double Trouble that May Underlie Airway Hyperresponsiveness in Asthma.

Am J Respir Cell Mol Biol. 2024-8

本文引用的文献

[1]
MERCURY-3: a randomized comparison of netarsudil/latanoprost and bimatoprost/timolol in open-angle glaucoma and ocular hypertension.

Graefes Arch Clin Exp Ophthalmol. 2024-1

[2]
Crossover Randomized Study of Pharmacologic Effects of Ripasudil-Brimonidine Fixed-Dose Combination Versus Ripasudil or Brimonidine.

Adv Ther. 2023-8

[3]
The anti-asthmatic potential of Rho-kinase inhibitor hydroxyfasudil in the model of experimentally induced allergic airway inflammation.

Eur J Pharmacol. 2023-1-5

[4]
Phase 2, Randomized, Open-Label Parallel-Group Study of Two Dosing Regimens of Netarsudil for the Treatment of Corneal Edema Due to Fuchs Corneal Dystrophy.

J Ocul Pharmacol Ther. 2022-12

[5]
IL-27 attenuates airway inflammation and epithelial-mesenchymal transition in allergic asthmatic mice possibly via the RhoA/ROCK signalling pathway.

Eur Cytokine Netw. 2022-3-1

[6]
Extracellular Matrix Stiffness in Lung Health and Disease.

Compr Physiol. 2022-6-29

[7]
Global Initiative for Asthma Strategy 2021: Executive Summary and Rationale for Key Changes.

Am J Respir Crit Care Med. 2022-1-1

[8]
Airway diameter at different transpulmonary pressures in ex vivo sheep lungs: implications for deep inspiration-induced bronchodilation and bronchoprotection.

Am J Physiol Lung Cell Mol Physiol. 2021-10-1

[9]
Belumosudil for chronic graft-versus-host disease after 2 or more prior lines of therapy: the ROCKstar Study.

Blood. 2021-12-2

[10]
Rho/ROCK-MYOCD in regulating airway smooth muscle growth and remodeling.

Am J Physiol Lung Cell Mol Physiol. 2021-7-1

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