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A ketogenic diet improves vascular hyperpermeability in type 2 diabetic mice by downregulating vascular pescadillo1 expression

The role of pescadillo1 (PES1) in regulating vascular permeability has been unknown. This study probes the role of PES1 and its mediated molecular mechanism in modulating vascular hyperpermeability in diabetic mice. Male C57BL/6J and db/db mice were fed a standard diet and a ketogenic diet (KD). Mea...

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Autores principales: Wang, Song, Zhou, Jielin, Lu, Jing, Lin, Yan, Liu, Shuaishuai, Chen, Keyang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10183701/
https://www.ncbi.nlm.nih.gov/pubmed/37060584
http://dx.doi.org/10.1111/jcmm.17744
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author Wang, Song
Zhou, Jielin
Lu, Jing
Lin, Yan
Liu, Shuaishuai
Chen, Keyang
author_facet Wang, Song
Zhou, Jielin
Lu, Jing
Lin, Yan
Liu, Shuaishuai
Chen, Keyang
author_sort Wang, Song
collection PubMed
description The role of pescadillo1 (PES1) in regulating vascular permeability has been unknown. This study probes the role of PES1 and its mediated molecular mechanism in modulating vascular hyperpermeability in diabetic mice. Male C57BL/6J and db/db mice were fed a standard diet and a ketogenic diet (KD). Meanwhile, mouse vascular endothelial cells (MVECs) were treated with β‐hydroxybutyric acid (β‐HB), Pes1 siRNA or a Pes1 overexpression plasmid. Additionally, knockout (KO) of Pes1 in mice was applied. After 12 weeks of feedings, enhanced vascular PES1 expression in diabetic mice was inhibited by the KD. The suppression of PES1 was also observed in β‐HB‐treated MVECs. In mice with Pes1 KO, the levels of vascular VEGF and PES1 were attenuated, while the levels of vascular VE‐cadherin, Ang‐1 and Occludin were upregulated. Similar outcomes also occurred after the knockdown of Pes1 in cultured MVECs, which were opposite to the effects induced by PES1 overexpression in MVECs. In vitro and in vivo experiments showed that high glucose concentration‐induced increases in vascular paracellular permeability declined after MVECs were treated by β‐HB or by knockdown of Pes1. In contrast, increases in vascular permeability were induced by overexpression of Pes1, which were suppressed by coadministration of β‐HB in cultured endothelial cells. Similarly declines in vascular permeability were found by Pes1 knockdown in diabetic mice. Mechanistically, β‐HB decreased PES1‐facilitated ubiquitination of VE‐cadherin. The KD suppressed the diabetes‐induced increase in PES1, which may result in vascular hyperpermeability through ubiquitination of VE‐cadherin in type 2 diabetic mice.
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spelling pubmed-101837012023-05-16 A ketogenic diet improves vascular hyperpermeability in type 2 diabetic mice by downregulating vascular pescadillo1 expression Wang, Song Zhou, Jielin Lu, Jing Lin, Yan Liu, Shuaishuai Chen, Keyang J Cell Mol Med Original Articles The role of pescadillo1 (PES1) in regulating vascular permeability has been unknown. This study probes the role of PES1 and its mediated molecular mechanism in modulating vascular hyperpermeability in diabetic mice. Male C57BL/6J and db/db mice were fed a standard diet and a ketogenic diet (KD). Meanwhile, mouse vascular endothelial cells (MVECs) were treated with β‐hydroxybutyric acid (β‐HB), Pes1 siRNA or a Pes1 overexpression plasmid. Additionally, knockout (KO) of Pes1 in mice was applied. After 12 weeks of feedings, enhanced vascular PES1 expression in diabetic mice was inhibited by the KD. The suppression of PES1 was also observed in β‐HB‐treated MVECs. In mice with Pes1 KO, the levels of vascular VEGF and PES1 were attenuated, while the levels of vascular VE‐cadherin, Ang‐1 and Occludin were upregulated. Similar outcomes also occurred after the knockdown of Pes1 in cultured MVECs, which were opposite to the effects induced by PES1 overexpression in MVECs. In vitro and in vivo experiments showed that high glucose concentration‐induced increases in vascular paracellular permeability declined after MVECs were treated by β‐HB or by knockdown of Pes1. In contrast, increases in vascular permeability were induced by overexpression of Pes1, which were suppressed by coadministration of β‐HB in cultured endothelial cells. Similarly declines in vascular permeability were found by Pes1 knockdown in diabetic mice. Mechanistically, β‐HB decreased PES1‐facilitated ubiquitination of VE‐cadherin. The KD suppressed the diabetes‐induced increase in PES1, which may result in vascular hyperpermeability through ubiquitination of VE‐cadherin in type 2 diabetic mice. John Wiley and Sons Inc. 2023-04-15 /pmc/articles/PMC10183701/ /pubmed/37060584 http://dx.doi.org/10.1111/jcmm.17744 Text en © 2023 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd. https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Articles
Wang, Song
Zhou, Jielin
Lu, Jing
Lin, Yan
Liu, Shuaishuai
Chen, Keyang
A ketogenic diet improves vascular hyperpermeability in type 2 diabetic mice by downregulating vascular pescadillo1 expression
title A ketogenic diet improves vascular hyperpermeability in type 2 diabetic mice by downregulating vascular pescadillo1 expression
title_full A ketogenic diet improves vascular hyperpermeability in type 2 diabetic mice by downregulating vascular pescadillo1 expression
title_fullStr A ketogenic diet improves vascular hyperpermeability in type 2 diabetic mice by downregulating vascular pescadillo1 expression
title_full_unstemmed A ketogenic diet improves vascular hyperpermeability in type 2 diabetic mice by downregulating vascular pescadillo1 expression
title_short A ketogenic diet improves vascular hyperpermeability in type 2 diabetic mice by downregulating vascular pescadillo1 expression
title_sort ketogenic diet improves vascular hyperpermeability in type 2 diabetic mice by downregulating vascular pescadillo1 expression
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10183701/
https://www.ncbi.nlm.nih.gov/pubmed/37060584
http://dx.doi.org/10.1111/jcmm.17744
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