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dc.contributor.authorMitra, Sumegha
dc.contributor.authorEpshtein, Yulia
dc.contributor.authorSammani, Saad
dc.contributor.authorQuijada, Hector
dc.contributor.authorChen, Weiguo
dc.contributor.authorBandela, Mounica
dc.contributor.authorDesai, Ankit A
dc.contributor.authorGarcia, Joe G N
dc.contributor.authorJacobson, Jeffrey R
dc.date.accessioned2021-04-19T21:46:08Z
dc.date.available2021-04-19T21:46:08Z
dc.date.issued2021-01-13
dc.identifier.citationMitra, S., Epshtein, Y., Sammani, S., Quijada, H., Chen, W., Bandela, M., ... & Jacobson, J. R. (2021). UCHL1, a deubiquitinating enzyme, regulates lung endothelial cell permeability in vitro and in vivo. American Journal of Physiology-Lung Cellular and Molecular Physiology, 320(4), L497-L507.en_US
dc.identifier.pmid33438509
dc.identifier.doi10.1152/ajplung.00492.2020
dc.identifier.urihttp://hdl.handle.net/10150/657816
dc.description.abstractIncreasing evidence suggests an important role for deubiquitinating enzymes (DUBs) in modulating a variety of biological functions and diseases. We previously identified the upregulation of the DUB ubiquitin carboxyl terminal hydrolase 1 (UCHL1) in murine ventilator-induced lung injury (VILI). However, the role of UCHL1 in modulating vascular permeability, a cardinal feature of acute lung injury (ALI) in general, remains unclear. We investigated the role of UCHL1 in pulmonary endothelial cell (EC) barrier function in vitro and in vivo and examined the effects of UCHL1 on VE-cadherin and claudin-5 regulation, important adherens and tight junctional components, respectively. Measurements of transendothelial electrical resistance confirmed decreased barrier enhancement induced by hepatocyte growth factor (HGF) and increased thrombin-induced permeability in both UCHL1-silenced ECs and in ECs pretreated with LDN-57444 (LDN), a pharmacological UCHL1 inhibitor. In addition, UCHL1 knockdown (siRNA) was associated with decreased expression of VE-cadherin and claudin-5, whereas silencing of the transcription factor FoxO1 restored claudin-5 levels. Finally, UCHL1 inhibition in vivo via LDN was associated with increased VILI in a murine model. These findings support a prominent functional role of UCHL1 in regulating lung vascular permeability via alterations in adherens and tight junctions and implicate UCHL1 as an important mediator of ALI.en_US
dc.language.isoenen_US
dc.publisherAmerican Physiological Societyen_US
dc.rightsCopyright © 2021 the American Physiological Society.en_US
dc.rights.urihttp://rightsstatements.org/vocab/InC/1.0/en_US
dc.subjectUCHL1en_US
dc.subjectVE-cadherinen_US
dc.subjectadherens junctionen_US
dc.subjectclaudin-5en_US
dc.subjectendothelial cellsen_US
dc.subjectlung vascular permeabilityen_US
dc.subjectTight Junctionen_US
dc.titleUCHL1, a deubiquitinating enzyme, regulates lung endothelial cell permeability in vitro and in vivoen_US
dc.typeArticleen_US
dc.identifier.eissn1522-1504
dc.contributor.departmentDepartment of Medicine, Arizona Health Sciences Center, University of Arizonaen_US
dc.identifier.journalAmerican journal of physiology. Lung cellular and molecular physiologyen_US
dc.description.note12 month embargo; published online 31 March 2021en_US
dc.description.collectioninformationThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at repository@u.library.arizona.edu.en_US
dc.eprint.versionFinal accepted manuscripten_US
dc.source.journaltitleAmerican journal of physiology. Lung cellular and molecular physiology
dc.source.volume320
dc.source.issue4
dc.source.beginpageL497
dc.source.endpageL507
dc.source.countryUnited States
dc.source.countryUnited States


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