@article{ff257d68be544bb6bb61e06c78a93ccb,
title = "LncRNA VEAL2 regulates PRKCB2 to modulate endothelial permeability in diabetic retinopathy",
abstract = "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 (veal2gib005Δ8/+) 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.",
keywords = "diabetic retinopathy, diacylglycerol, endothelial permeability, long non-coding RNA, protein kinase C beta",
author = "Paras Sehgal and Samatha Mathew and Ambily Sivadas and Arjun Ray and Jyoti Tanwar and Sushma Vishwakarma and Gyan Ranjan and Shamsudheen, {K V} and Bhoyar, {Rahul C} and Abhishek Pateria and Elvin Leonard and Mukesh Lalwani and Archana Vats and Pappuru, {Rajeev R} and Mudit Tyagi and Saumya Jakati and Shantanu Sengupta and {B K}, Binukumar and Subhabrata Chakrabarti and Inderjeet Kaur and Motiani, {Rajender K} and Vinod Scaria and Sridhar Sivasubbu",
note = "Funding Information: The authors thank Drs. Souvik Maiti, Vivek Natarajan, and Manikandan Subramanian for critical comments on the manuscript. We acknowledge the contributions of Ankit Verma and Rijith Jayarajan for help with RNA sequencing experiments. We thank Drs. Kriti Kaushik and Shruti Kapoor for help with the initial bioinformatic analyses. We thank Shadabul Haque for his contributions toward the morpholino standardization experiments in zebrafish and Yusman Manchanda for help with maintaining zebrafish lines. The authors acknowledge kind gifts from Dr. Kausik Chakraborty for GFP protein and Dr. Vivek Natarajan for ‐cloned plasmid. The authors also acknowledge Mr. Manish Kumar for technical assistance in confocal microscopy. This work was generously supported by the Council of Scientific and Industrial Research (CSIR), India, through the grants BSC0123, MLP1801, and BSC0403 for imaging facility. PS, SM, and AS acknowledge their Senior Research Fellowships from CSIR, India and SV acknowledges support from Manipal Academy of Higher Education in Manipal, India towards her PhD. RKM acknowledges Regional Centre for Biotechnology for Institutional Core funding and Science & Engineering Research Board (SERB) Start‐up Research Grant (SRG/2019/000495), Department of Science and Technology, India. IK and SC were supported by the Department of Biotechnology, India (BT/01/COE/06/02/10 and BT/PR32404/MED/30/2136/2019). mitfa‐e‐GFP Publisher Copyright: {\textcopyright} 2021 The Authors. Published under the terms of the CC BY 4.0 license",
year = "2021",
month = aug,
day = "2",
doi = "10.15252/embj.2020107134",
language = "English",
volume = "40",
journal = "EMBO Journal",
issn = "0261-4189",
publisher = "Wiley-Blackwell",
number = "15",
}