Search: onr:"swepub:oai:DiVA.org:uu-487895" >
Claudin5 protects t...
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Richards, MarkUppsala universitet,Science for Life Laboratory, SciLifeLab,Vaskulärbiologi,Uppsala Univ, Beijer Gene & Neuro Lab, Uppsala, Sweden.
(author)
Claudin5 protects the peripheral endothelial barrier in an organ and vessel-type-specific manner
- Article/chapterEnglish2022
Publisher, publication year, extent ...
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eLife Sciences Publications Ltd,2022
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electronicrdacarrier
Numbers
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LIBRIS-ID:oai:DiVA.org:uu-487895
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https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-487895URI
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https://doi.org/10.7554/eLife.78517DOI
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http://kipublications.ki.se/Default.aspx?queryparsed=id:150919633URI
Supplementary language notes
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Language:English
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Summary in:English
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Subject category:ref swepub-contenttype
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Subject category:art swepub-publicationtype
Notes
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Dysfunctional and leaky blood vessels resulting from disruption of the endothelial cell (EC) barrier accompanies numerous diseases. The EC barrier is established through endothelial cell tight and adherens junctions. However, the expression pattern and precise contribution of different junctional proteins to the EC barrier is poorly understood. Here, we focus on organs with continuous endothelium to identify structural and functional in vivo characteristics of the EC barrier. Assembly of multiple single-cell RNAseq datasets into a single integrated database revealed the variability and commonalities of EC barrier patterning. Across tissues, Claudin5 exhibited diminishing expression along the arteriovenous axis, correlating with EC barrier integrity. Functional analysis identified tissue-specific differences in leakage properties and response to the leakage agonist histamine. Loss of Claudin5 enhanced histamine-induced leakage in an organotypic and vessel type-specific manner in an inducible, EC-specific, knock-out mouse. Mechanistically, Claudin5 loss left junction ultrastructure unaffected but altered its composition, with concomitant loss of zonula occludens-1 and upregulation of VE-Cadherin expression. These findings uncover the organ-specific organisation of the EC barrier and distinct importance of Claudin5 in different vascular beds, providing insights to modify EC barrier stability in a targeted, organ-specific manner.
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Added entries (persons, corporate bodies, meetings, titles ...)
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Nwadozi, EmmanuelUppsala universitet,Vaskulärbiologi,Science for Life Laboratory, SciLifeLab,Uppsala Univ, Beijer Gene & Neuro Lab, Uppsala, Sweden.(Swepub:uu)emmnw220
(author)
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Pal, SagnikUppsala universitet,Vaskulärbiologi,Science for Life Laboratory, SciLifeLab,Uppsala Univ, Beijer Gene & Neuro Lab, Uppsala, Sweden.(Swepub:uu)sagpa140
(author)
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Martinsson, PernillaUppsala universitet,Science for Life Laboratory, SciLifeLab,Vaskulärbiologi,Uppsala Univ, Beijer Gene & Neuro Lab, Uppsala, Sweden.(Swepub:uu)pernmart
(author)
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Kaakinen, MikaUniv Oulu, Fac Biochem & Mol Med, Oulu Ctr Cell Matrix Res, Bioctr Oulu, Oulu, Finland.
(author)
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Gloger, MarleenUppsala universitet,Vaskulärbiologi,Science for Life Laboratory, SciLifeLab,Uppsala Univ, Beijer Gene & Neuro Lab, Uppsala, Sweden.(Swepub:uu)margl916
(author)
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Sjöberg, ElinUppsala universitet,Science for Life Laboratory, SciLifeLab,Vaskulärbiologi,Uppsala Univ, Beijer Gene & Neuro Lab, Uppsala, Sweden.(Swepub:uu)elisj828
(author)
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Koltowska, KatarzynaUppsala universitet,Vaskulärbiologi,Science for Life Laboratory, SciLifeLab,Uppsala Univ, Beijer Gene & Neuro Lab, Uppsala, Sweden.(Swepub:uu)katko745
(author)
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Betsholtz, ChristerUppsala universitet,Vaskulärbiologi,Karolinska Inst, Dept Med Huddinge, Campus Flemingsberg, Huddinge, Sweden.(Swepub:uu)chbet517
(author)
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Eklund, LauriUniv Oulu, Fac Biochem & Mol Med, Oulu Ctr Cell Matrix Res, Bioctr Oulu, Oulu, Finland.
(author)
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Nordling, Sofia,1985-Uppsala universitet,Science for Life Laboratory, SciLifeLab,Vaskulärbiologi,Uppsala Univ, Beijer Gene & Neuro Lab, Uppsala, Sweden.(Swepub:uu)sofno833
(author)
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Claesson-Welsh, LenaUppsala universitet,Science for Life Laboratory, SciLifeLab,Vaskulärbiologi,Uppsala Univ, Beijer Gene & Neuro Lab, Uppsala, Sweden.(Swepub:uu)lcl04207
(author)
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Uppsala universitetScience for Life Laboratory, SciLifeLab
(creator_code:org_t)
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