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LncRNA VEAL2 regulates PRKCB2 to modulate endothelial permeability in diabetic retinopathy
Long non‐coding RNAs (lncRNAs) are emerging as key regulators of endothelial cell function. Here, we investigated the role of a novel vascular endothelial‐associated lncRNA (VEAL2) in regulating endothelial permeability. Precise editing of veal2 loci in zebrafish (veal2 (gib005Δ8/+)) induced cranial...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8327952/ https://www.ncbi.nlm.nih.gov/pubmed/34180064 http://dx.doi.org/10.15252/embj.2020107134 |
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author | Sehgal, Paras Mathew, Samatha Sivadas, Ambily Ray, Arjun Tanwar, Jyoti Vishwakarma, Sushma Ranjan, Gyan Shamsudheen, K V Bhoyar, Rahul C Pateria, Abhishek Leonard, Elvin Lalwani, Mukesh Vats, Archana Pappuru, Rajeev R Tyagi, Mudit Jakati, Saumya Sengupta, Shantanu B K, Binukumar Chakrabarti, Subhabrata Kaur, Inderjeet Motiani, Rajender K Scaria, Vinod Sivasubbu, Sridhar |
author_facet | Sehgal, Paras Mathew, Samatha Sivadas, Ambily Ray, Arjun Tanwar, Jyoti Vishwakarma, Sushma Ranjan, Gyan Shamsudheen, K V Bhoyar, Rahul C Pateria, Abhishek Leonard, Elvin Lalwani, Mukesh Vats, Archana Pappuru, Rajeev R Tyagi, Mudit Jakati, Saumya Sengupta, Shantanu B K, Binukumar Chakrabarti, Subhabrata Kaur, Inderjeet Motiani, Rajender K Scaria, Vinod Sivasubbu, Sridhar |
author_sort | Sehgal, Paras |
collection | PubMed |
description | Long non‐coding RNAs (lncRNAs) are emerging as key regulators of endothelial cell function. Here, we investigated the role of a novel vascular endothelial‐associated lncRNA (VEAL2) in regulating endothelial permeability. Precise editing of veal2 loci in zebrafish (veal2 (gib005Δ8/+)) induced cranial hemorrhage. In vitro and in vivo studies revealed that veal2 competes with diacylglycerol for interaction with protein kinase C beta‐b (Prkcbb) and regulates its kinase activity. Using PRKCB2 as bait, we identified functional ortholog of veal2 in humans from HUVECs and named it as VEAL2. Overexpression and knockdown of VEAL2 affected tubulogenesis and permeability in HUVECs. VEAL2 was differentially expressed in choroid tissue in eye and blood from patients with diabetic retinopathy, a disease where PRKCB2 is known to be hyperactivated. Further, VEAL2 could rescue the effects of PRKCB2‐mediated turnover of endothelial junctional proteins thus reducing hyperpermeability in hyperglycemic HUVEC model of diabetic retinopathy. Based on evidence from zebrafish and hyperglycemic HUVEC models and diabetic retinopathy patients, we report a hitherto unknown VEAL2 lncRNA‐mediated regulation of PRKCB2, for modulating junctional dynamics and maintenance of endothelial permeability. |
format | Online Article Text |
id | pubmed-8327952 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-83279522021-08-15 LncRNA VEAL2 regulates PRKCB2 to modulate endothelial permeability in diabetic retinopathy Sehgal, Paras Mathew, Samatha Sivadas, Ambily Ray, Arjun Tanwar, Jyoti Vishwakarma, Sushma Ranjan, Gyan Shamsudheen, K V Bhoyar, Rahul C Pateria, Abhishek Leonard, Elvin Lalwani, Mukesh Vats, Archana Pappuru, Rajeev R Tyagi, Mudit Jakati, Saumya Sengupta, Shantanu B K, Binukumar Chakrabarti, Subhabrata Kaur, Inderjeet Motiani, Rajender K Scaria, Vinod Sivasubbu, Sridhar EMBO J Articles Long non‐coding RNAs (lncRNAs) are emerging as key regulators of endothelial cell function. Here, we investigated the role of a novel vascular endothelial‐associated lncRNA (VEAL2) in regulating endothelial permeability. Precise editing of veal2 loci in zebrafish (veal2 (gib005Δ8/+)) induced cranial hemorrhage. In vitro and in vivo studies revealed that veal2 competes with diacylglycerol for interaction with protein kinase C beta‐b (Prkcbb) and regulates its kinase activity. Using PRKCB2 as bait, we identified functional ortholog of veal2 in humans from HUVECs and named it as VEAL2. Overexpression and knockdown of VEAL2 affected tubulogenesis and permeability in HUVECs. VEAL2 was differentially expressed in choroid tissue in eye and blood from patients with diabetic retinopathy, a disease where PRKCB2 is known to be hyperactivated. Further, VEAL2 could rescue the effects of PRKCB2‐mediated turnover of endothelial junctional proteins thus reducing hyperpermeability in hyperglycemic HUVEC model of diabetic retinopathy. Based on evidence from zebrafish and hyperglycemic HUVEC models and diabetic retinopathy patients, we report a hitherto unknown VEAL2 lncRNA‐mediated regulation of PRKCB2, for modulating junctional dynamics and maintenance of endothelial permeability. John Wiley and Sons Inc. 2021-06-28 2021-08-02 /pmc/articles/PMC8327952/ /pubmed/34180064 http://dx.doi.org/10.15252/embj.2020107134 Text en © 2021 The Authors. Published under the terms of the CC BY 4.0 license 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 | Articles Sehgal, Paras Mathew, Samatha Sivadas, Ambily Ray, Arjun Tanwar, Jyoti Vishwakarma, Sushma Ranjan, Gyan Shamsudheen, K V Bhoyar, Rahul C Pateria, Abhishek Leonard, Elvin Lalwani, Mukesh Vats, Archana Pappuru, Rajeev R Tyagi, Mudit Jakati, Saumya Sengupta, Shantanu B K, Binukumar Chakrabarti, Subhabrata Kaur, Inderjeet Motiani, Rajender K Scaria, Vinod Sivasubbu, Sridhar LncRNA VEAL2 regulates PRKCB2 to modulate endothelial permeability in diabetic retinopathy |
title | LncRNA VEAL2 regulates PRKCB2 to modulate endothelial permeability in diabetic retinopathy |
title_full | LncRNA VEAL2 regulates PRKCB2 to modulate endothelial permeability in diabetic retinopathy |
title_fullStr | LncRNA VEAL2 regulates PRKCB2 to modulate endothelial permeability in diabetic retinopathy |
title_full_unstemmed | LncRNA VEAL2 regulates PRKCB2 to modulate endothelial permeability in diabetic retinopathy |
title_short | LncRNA VEAL2 regulates PRKCB2 to modulate endothelial permeability in diabetic retinopathy |
title_sort | lncrna veal2 regulates prkcb2 to modulate endothelial permeability in diabetic retinopathy |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8327952/ https://www.ncbi.nlm.nih.gov/pubmed/34180064 http://dx.doi.org/10.15252/embj.2020107134 |
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