Regulation of specific connexins differentially alters gap junction permeability and endothelial cell function

While many have explored how vascular processes alter gap junction communication and composition few have analyzed the role of specific gap junction connexin proteins in regulating cellular communication and wound healing. Using RNA interference or peptide inhibitors to downregulate specific connexins we examined the role of gap junctions in intercellular diffusion, calcium excitation, and in mediating the expression of vascular regulators transforming growth factor-[Beta][ (TGF-[beta]), prostacyclin, and endothelial nitric oxide synthase (eNOS). siRNA inhibition of connexin 43 in porcine aortic endothelial cells (PAEC) significantly decreased the diffusion distance of Lucifer yellow dye and cytoplasmic calcium levels after mechanical wounding. Wound healing experiments suggested that stimulatory signals travel through gap junctions containing connexin 43, while inhibitory signal travel through gap junctions containing connexin 37. Connexin 43 and connexin 37 inhibition, alone or in combination, reduced the levels of secreted latent TGF-[beta] in confluent PAEC monolayers after 24 hours of incubation. Human umbilical vein endothelial cells (HUVEC) behaved in a similar manner. Inhibition of any one of the three connexins resulted in a marked increase in eNOS concentration.

Department dc:contributor.department

Massachusetts Institute of Technology. Biological Engineering Division.

Grantor dc:publisher

Massachusetts Institute of Technology

Year dc:date.issued

2006

Author dc:creator

• Elihu, David Morad

Advisor dc:contributor.advisor

• Elazer R. Edelman.

• Biological Engineering Division.

Statement dc:rights

• MIT theses are protected by copyright. They may be viewed, downloaded, or printed from this source but further reproduction or distribution in any format is prohibited without written permission.

Licence dc:rights.uri

• http://dspace.mit.edu/handle/1721.1/7582

Language dc:language.iso

eng

Handle dc:identifier.uri

http://hdl.handle.net/1721.1/37974

OAI identifier oai:identifier

oai:dspace.mit.edu:1721.1/37974