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LncRNA VEAL2 regulates PRKCB2 to modulate endothelial permeability in diabetic retinopathy
Author(s) -
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
Publication year - 2021
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.15252/embj.2020107134
Subject(s) - biology , diabetic retinopathy , diabetes mellitus , retinopathy , microbiology and biotechnology , endocrinology
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 ( 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.