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http://purl.uniprot.org/citations/29295866 | http://www.w3.org/2000/01/rdf-schema#comment | "Familial cerebral cavernous malformations type III (fCCM3) is a disease of the cerebrovascular system caused by loss-of-function mutations in ccm3 that result in dilated capillary beds that are susceptible to hemorrhage. Before hemorrhage, fCCM3 lesions are characterized by a hyperpermeable blood-brain barrier (BBB), the key pathologic feature of fCCM3. We demonstrate that connexin 43 (Cx43), a gap junction (GJ) protein that is incorporated into the BBB junction complex, is up-regulated in lesions of a murine model of fCCM3. Small interfering RNA-mediated ccm3 knockdown (CCM3KD) in brain endothelial cells in vitro increased Cx43 protein expression, GJ plaque size, GJ intracellular communication (GJIC), and barrier permeability. CCM3KD hyperpermeability was rescued by GAP27, a peptide gap junction and hemichannel inhibitor of Cx43 GJIC. Tight junction (TJ) protein, zonula occludens 1 (ZO-1), accumulated at Cx43 GJs in CCM3KD cells and displayed fragmented staining at TJs. The GAP27-mediated inhibition of Cx43 GJs in CCM3KD cells restored ZO-1 to TJ structures and reduced plaque accumulation at Cx43 GJs. The TJ protein, Claudin-5, was also fragmented at TJs in CCM3KD cells, and GAP27 treatment lengthened TJ-associated fragments and increased Claudin 5-Claudin 5 transinteraction. Overall, we demonstrate that Cx43 GJs are aberrantly increased in fCCM3 and regulate barrier permeability by a TJ-dependent mechanism.-Johnson, A. M., Roach, J. P., Hu, A., Stamatovic, S. M., Zochowski, M. R., Keep, R. F., Andjelkovic, A. V. Connexin 43 gap junctions contribute to brain endothelial barrier hyperpermeability in familial cerebral cavernous malformations type III by modulating tight junction structure."xsd:string |
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http://purl.uniprot.org/citations/29295866 | http://purl.uniprot.org/core/author | "Johnson A.M."xsd:string |
http://purl.uniprot.org/citations/29295866 | http://purl.uniprot.org/core/author | "Hu A."xsd:string |
http://purl.uniprot.org/citations/29295866 | http://purl.uniprot.org/core/author | "Keep R.F."xsd:string |
http://purl.uniprot.org/citations/29295866 | http://purl.uniprot.org/core/author | "Andjelkovic A.V."xsd:string |
http://purl.uniprot.org/citations/29295866 | http://purl.uniprot.org/core/author | "Stamatovic S.M."xsd:string |
http://purl.uniprot.org/citations/29295866 | http://purl.uniprot.org/core/author | "Roach J.P."xsd:string |
http://purl.uniprot.org/citations/29295866 | http://purl.uniprot.org/core/author | "Zochowski M.R."xsd:string |
http://purl.uniprot.org/citations/29295866 | http://purl.uniprot.org/core/date | "2018"xsd:gYear |
http://purl.uniprot.org/citations/29295866 | http://purl.uniprot.org/core/name | "FASEB J"xsd:string |
http://purl.uniprot.org/citations/29295866 | http://purl.uniprot.org/core/pages | "2615-2629"xsd:string |
http://purl.uniprot.org/citations/29295866 | http://purl.uniprot.org/core/title | "Connexin 43 gap junctions contribute to brain endothelial barrier hyperpermeability in familial cerebral cavernous malformations type III by modulating tight junction structure."xsd:string |
http://purl.uniprot.org/citations/29295866 | http://purl.uniprot.org/core/volume | "32"xsd:string |
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