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Vascular permeabili...
Vascular permeability in retinopathy is regulated by VEGFR2 Y949 signaling to VE-cadherin
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- Smith, Ross O. (author)
- Uppsala universitet,Science for Life Laboratory, SciLifeLab,Institutionen för immunologi, genetik och patologi,Uppsala Univ, Rudbeck Lab, Uppsala, Sweden.
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- Ninchoji, Takeshi (author)
- Uppsala universitet,Institutionen för immunologi, genetik och patologi,Science for Life Laboratory, SciLifeLab,Uppsala Univ, Rudbeck Lab, Uppsala, Sweden.
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- Gordon, Emma (author)
- Uppsala universitet,Science for Life Laboratory, SciLifeLab,Institutionen för immunologi, genetik och patologi,Uppsala Univ, Rudbeck Lab, Uppsala, Sweden.
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- Andre, Helder (author)
- Karolinska Institutet
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- Dejana, Elisabetta (author)
- Uppsala universitet,Institutionen för immunologi, genetik och patologi,Science for Life Laboratory, SciLifeLab,Uppsala Univ, Rudbeck Lab, Uppsala, Sweden.;IFOM IEO, Campus Via Adamello, Milan, Italy.
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- Vestweber, Dietmar (author)
- Max Planck Inst Mol Biomed, Munster, Germany.
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- Kvanta, Anders (author)
- Karolinska Institutet
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- Claesson-Welsh, Lena (author)
- Uppsala universitet,Science for Life Laboratory, SciLifeLab,Institutionen för immunologi, genetik och patologi,Uppsala Univ, Rudbeck Lab, Uppsala, Sweden.
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(creator_code:org_t)
- ELIFE SCIENCES PUBLICATIONS LTD, 2020
- 2020
- English.
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In: eLIFE. - : ELIFE SCIENCES PUBLICATIONS LTD. - 2050-084X. ; 9
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https://doi.org/10.7...
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https://uu.diva-port... (primary) (Raw object)
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Abstract
Subject headings
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- Edema stemming from leaky blood vessels is common in eye diseases such as agerelated macular degeneration and diabetic retinopathy. Whereas therapies targeting vascular endothelial growth factor A (VEGFA) can suppress leakage, side-effects include vascular rarefaction and geographic atrophy. By challenging mouse models representing different steps in VEGFA/VEGF receptor 2 (VEGFR2)-induced vascular permeability, we show that targeting signaling downstream of VEGFR2 pY949 limits vascular permeability in retinopathy induced by high oxygen or by laser-wounding. Although suppressed permeability is accompanied by reduced pathological neoangiogenesis in oxygen-induced retinopathy, similarly sized lesions leak less in mutant mice, separating regulation of permeability from angiogenesis. Strikingly, vascular endothelial (VE)-cadherin phosphorylation at the Y685, but not Y658, residue is reduced when VEGFR2 pY949 signaling is impaired. These findings support a mechanism whereby VE-cadherin Y685 phosphorylation is selectively associated with excessive vascular leakage. Therapeutically, targeting VEGFR2-regulated VE-cadherin phosphorylation could suppress edema while leaving other VEGFR2-dependent functions intact.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)
Publication and Content Type
- ref (subject category)
- art (subject category)
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