PUBLICATION
LncRNA VEAL2 regulates PRKCB2 to modulate endothelial permeability in diabetic retinopathy
- Authors
- Sehgal, P., Mathew, S., Sivadas, A., Ray, A., Tanwar, J., Vishwakarma, S., Ranjan, G., Shamsudheen, K.V., Bhoyar, R.C., Pateria, A., Leonard, E., Lalwani, M., Vats, A., Pappuru, R.R., Tyagi, M., Jakati, S., Sengupta, S., B K, B., Chakrabarti, S., Kaur, I., Motiani, R.K., Scaria, V., Sivasubbu, S.
- ID
- ZDB-PUB-210629-39
- Date
- 2021
- Source
- The EMBO journal 40(15): e107134 (Journal)
- Registered Authors
- Sivasubbu, Sridhar
- Keywords
- diabetic retinopathy, diacylglycerol, endothelial permeability, long non-coding RNA, protein kinase C beta
- MeSH Terms
-
- Aged
- Aged, 80 and over
- Animals
- Animals, Genetically Modified
- Case-Control Studies
- Diabetic Retinopathy/genetics*
- Diabetic Retinopathy/physiopathology
- Embryo, Nonmammalian
- Endothelium, Vascular
- Gene Expression Regulation
- Human Umbilical Vein Endothelial Cells
- Humans
- Middle Aged
- Permeability
- Protein Kinase C beta/genetics*
- Protein Kinase C beta/metabolism
- RNA, Long Noncoding/blood
- RNA, Long Noncoding/genetics*
- Zebrafish/embryology
- Zebrafish/genetics*
- Zebrafish Proteins/genetics
- Zebrafish Proteins/metabolism
- PubMed
- 34180064 Full text @ EMBO J.
Citation
Sehgal, P., Mathew, S., Sivadas, A., Ray, A., Tanwar, J., Vishwakarma, S., Ranjan, G., Shamsudheen, K.V., Bhoyar, R.C., Pateria, A., Leonard, E., Lalwani, M., Vats, A., Pappuru, R.R., Tyagi, M., Jakati, S., Sengupta, S., B K, B., Chakrabarti, S., Kaur, I., Motiani, R.K., Scaria, V., Sivasubbu, S. (2021) LncRNA VEAL2 regulates PRKCB2 to modulate endothelial permeability in diabetic retinopathy. The EMBO journal. 40(15):e107134.
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping