Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2021
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
_version_ 1783732208623681536
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
work_keys_str_mv AT sehgalparas lncrnaveal2regulatesprkcb2tomodulateendothelialpermeabilityindiabeticretinopathy
AT mathewsamatha lncrnaveal2regulatesprkcb2tomodulateendothelialpermeabilityindiabeticretinopathy
AT sivadasambily lncrnaveal2regulatesprkcb2tomodulateendothelialpermeabilityindiabeticretinopathy
AT rayarjun lncrnaveal2regulatesprkcb2tomodulateendothelialpermeabilityindiabeticretinopathy
AT tanwarjyoti lncrnaveal2regulatesprkcb2tomodulateendothelialpermeabilityindiabeticretinopathy
AT vishwakarmasushma lncrnaveal2regulatesprkcb2tomodulateendothelialpermeabilityindiabeticretinopathy
AT ranjangyan lncrnaveal2regulatesprkcb2tomodulateendothelialpermeabilityindiabeticretinopathy
AT shamsudheenkv lncrnaveal2regulatesprkcb2tomodulateendothelialpermeabilityindiabeticretinopathy
AT bhoyarrahulc lncrnaveal2regulatesprkcb2tomodulateendothelialpermeabilityindiabeticretinopathy
AT pateriaabhishek lncrnaveal2regulatesprkcb2tomodulateendothelialpermeabilityindiabeticretinopathy
AT leonardelvin lncrnaveal2regulatesprkcb2tomodulateendothelialpermeabilityindiabeticretinopathy
AT lalwanimukesh lncrnaveal2regulatesprkcb2tomodulateendothelialpermeabilityindiabeticretinopathy
AT vatsarchana lncrnaveal2regulatesprkcb2tomodulateendothelialpermeabilityindiabeticretinopathy
AT pappururajeevr lncrnaveal2regulatesprkcb2tomodulateendothelialpermeabilityindiabeticretinopathy
AT tyagimudit lncrnaveal2regulatesprkcb2tomodulateendothelialpermeabilityindiabeticretinopathy
AT jakatisaumya lncrnaveal2regulatesprkcb2tomodulateendothelialpermeabilityindiabeticretinopathy
AT senguptashantanu lncrnaveal2regulatesprkcb2tomodulateendothelialpermeabilityindiabeticretinopathy
AT bkbinukumar lncrnaveal2regulatesprkcb2tomodulateendothelialpermeabilityindiabeticretinopathy
AT chakrabartisubhabrata lncrnaveal2regulatesprkcb2tomodulateendothelialpermeabilityindiabeticretinopathy
AT kaurinderjeet lncrnaveal2regulatesprkcb2tomodulateendothelialpermeabilityindiabeticretinopathy
AT motianirajenderk lncrnaveal2regulatesprkcb2tomodulateendothelialpermeabilityindiabeticretinopathy
AT scariavinod lncrnaveal2regulatesprkcb2tomodulateendothelialpermeabilityindiabeticretinopathy
AT sivasubbusridhar lncrnaveal2regulatesprkcb2tomodulateendothelialpermeabilityindiabeticretinopathy