miR-144-mediated Inhibition of ROCK1 Protects against LPS-induced Lung Endothelial Hyperpermeability

American Journal of Respiratory Cell and Molecular Biology
M Rizwan SiddiquiThomas P Shanley

Abstract

Dysfunctional endothelial cell (EC) barrier and increased lung vascular permeability is a cardinal feature of acute lung injury and sepsis that may result in a pathophysiological condition characterized by alveolar flooding, pulmonary edema, and subsequent hypoxemia. In lung ECs, activation of Rho-associated kinase-1 (ROCK1) phosphorylates myosin light chain (MLC)-associated phosphatase at its inhibitory site, which favors phosphorylation of MLC, stress fiber formation, and hyperpermeability during acute lung injury. The role of microRNA-144 (miR-144) has been well investigated in many human diseases, including cardiac ischemia/reperfusion-induced injury, lung cancer, and lung viral infection; however, its role in pulmonary EC barrier regulation remains obscure. Here, we investigated the miR-144-mediated mechanism in the protection of endothelial barrier function in an LPS-induced lung injury model. By using transendothelial electrical resistance and transwell permeability assay to examine in vitro permeability and immunofluorescence microscopy to determine barrier integrity, we showed that ectopic expression of miR-144 effectively blocked lung EC barrier disruption and hyperpermeability in response to proinflammatory agents. F...Continue Reading

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Citations

Mar 17, 2020·American Journal of Respiratory and Critical Care Medicine·Yaseen M ArabiHasan M Al-Dorzi
Nov 19, 2019·Biotechnology and Applied Biochemistry·Xianjie ZhangYuKai Zhou
Apr 3, 2020·The Kaohsiung Journal of Medical Sciences·Jian ZhangYin Liang
Dec 11, 2020·The Journal of Biological Chemistry·Sandip M Swain, Rodger A Liddle
Aug 3, 2021·Molecular and Cellular Biochemistry·Xiaolei GongHaibo Zhang
Aug 28, 2021·Cells·Maria Luísa da Silveira Hahmeyer, José Eduardo da Silva-Santos

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Methods Mentioned

BETA
GTPases
Assay
transfection

Software Mentioned

Targetscan
ImageJ
GraphPad Prism
GraphPad
mirdb
miRanda

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