Sehgal, Paras and Mathew, Samatha and Sivadas, Ambily and Ray, Arjun and Tanwar, Jyoti and Vishwakarma, Sushma and Ranjan, Gyan and Shamsudheen, K V and Bhoyar, Rahul C and Pateria, Abhishek and Leonard, Elvin and Lalwani, Mukesh and Vats, Archana and Pappuru, Rajeev R and Tyagi, Mudit and Jakati, Saumya and Sengupta, Shantanu and B K, Binukumar and Chakrabarti, Subhabrata and Kaur, Inderjeet and Motiani, Rajender K and Scaria, Vinod and Sivasubbu, Sridhar (2021) LncRNA VEAL2 regulates PRKCB2 to modulate endothelial permeability in diabetic retinopathy. The EMBO Journal. ISSN 0261-4189

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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.

Item Type:	Article
Subjects:	Biomedical Science
Depositing User:	RCB Library
Date Deposited:	29 Jul 2021 07:48
Last Modified:	29 Jul 2021 07:48
URI:	http://rcb.sciencecentral.in/id/eprint/617

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