LncRNA VEAL2 regulates PRKCB2 to modulate endothelial permeability in diabetic retinopathy

Paras Sehgal, Samatha Mathew, Ambily Sivadas, Arjun Ray, Jyoti Tanwar, Sushma Vishwakarma, Gyan Ranjan, K V Shamsudheen, Rahul C Bhoyar, Abhishek Pateria, Elvin Leonard, Mukesh Lalwani, Archana Vats, Rajeev R Pappuru, Mudit Tyagi, Saumya Jakati, Shantanu Sengupta, Binukumar B K, Subhabrata Chakrabarti, Inderjeet KaurRajender K Motiani, Vinod Scaria*, Sridhar Sivasubbu*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

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.

Original languageEnglish
Article numbere107134
JournalEMBO Journal
Issue number15
Early online date28 Jun 2021
Publication statusPublished - 2 Aug 2021

Keywords / Materials (for Non-textual outputs)

  • diabetic retinopathy
  • diacylglycerol
  • endothelial permeability
  • long non-coding RNA
  • protein kinase C beta


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