Por favor, use este identificador para citar o enlazar a este item: http://hdl.handle.net/10261/150423
COMPARTIR / EXPORTAR:
logo share SHARE logo core CORE BASE
Visualizar otros formatos: MARC | Dublin Core | RDF | ORE | MODS | METS | DIDL | DATACITE

Invitar a revisión por pares abierta
Título

Activation of Rac1 and Rhoa preserve corneal endothelial barrier function

AutorOrtega, María C.; Santander-García, Diana; Marcos Ramiro, Beatriz CSIC; Barroso, Susana CSIC; Cox, Susan; Jiménez-Alfaro, Ignacio CSIC; Millán, Jaime CSIC ORCID
Palabras claveBarrier function
ROCK
RhoA
Osmotic stress
Rac1
Fecha de publicación4-oct-2016
CitaciónInvestigative ophthalmology & visual science 57: 6210- 6222 (2016)
ResumenPURPOSE. The corneal endothelium is responsible for the correct hydration of the corneal stroma. Corneal endothelial cells have a low proliferative capacity, so preserving their barrier function under suboptimal conditions that cause osmotic imbalance, such as those arising from corneal pathologies, age, cryopreservation, and transplantation, is essential for maintaining corneal transparency. We have investigated the signaling induced by hyperosmotic shock that reversibly disrupts corneal endothelial barriers in human endothelial cells and in murine corneas. METHODS. Endothelial barrier properties were analyzed in vitro by electric cell substrate impedance sensing (ECIS) and confocal microscopy of the human endothelial cell line B4G12-HCEC, and, ex vivo, by confocal microscopy and stimulated emission-depletion (STED) superresolution microscopy of murine corneas. Cell signaling in response to hyperosmotic stress, induced with an excess of sodium chloride, was investigated in B4G12-HCECs. Rho GTPase activity was detected by pulldown assays with recombinant GST proteins fused to the Rho binding domains of Rho effectors. RESULTS. Hyperosmotic stress increased actin polymerization and activated the Rho GTPases Rac1 and RhoA, but not Cdc42. Rac1-and RhoA-mediated pathway inhibition had a minor effect on barrier disruption but partially delayed barrier reformation after stress withdrawal. In contrast, Rac1 and RhoA activation enhanced constitutive endothelial barrier function and accelerated barrier repair. CONCLUSIONS. Our results indicate that Rac1 and RhoA activation do not mediate stress-induced cell contraction but are endothelial responses that act to restore and maintain barrier homeostasis. Therefore, pharmacological activation of these two GTPases could be a therapeutic strategy for preserving corneal endothelial barrier function.
URIhttp://hdl.handle.net/10261/150423
DOI10.1167/iovs.16-20031
Identificadoresdoi: 10.1167/iovs.16-20031
issn: 1552-5783
Aparece en las colecciones: (CBM) Artículos




Ficheros en este ítem:
Fichero Descripción Tamaño Formato
MillánJ_ActivationOfRac1AndRhoAPreserve.pdf2,36 MBAdobe PDFVista previa
Visualizar/Abrir
Mostrar el registro completo

CORE Recommender

PubMed Central
Citations

8
checked on 17-mar-2024

SCOPUSTM   
Citations

12
checked on 20-mar-2024

WEB OF SCIENCETM
Citations

11
checked on 28-feb-2024

Page view(s)

358
checked on 28-mar-2024

Download(s)

400
checked on 28-mar-2024

Google ScholarTM

Check

Altmetric

Altmetric


Artículos relacionados:


Este item está licenciado bajo una Licencia Creative Commons Creative Commons