LncRNA TAAL is a Modulator of Tie1-Mediated Vascular Function in Diabetic Retinopathy DOI Creative Commons
Gyan Ranjan,

Samriddhi Arora,

Sarmeela Sharma

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Сен. 14, 2024

Diabetic retinopathy (DR), a leading cause of vision impairment and blindness, is characterized by abnormal retinal vascular changes due to chronic hyperglycemia. The Tie-1 signaling pathway, essential for growth remodeling, has emerged as key therapeutic target, though its molecular mechanisms interactome remain largely unclear. Through protein-centric approach, we identified novel lncRNA named it Tie1-associated angiogenic (TAAL). TAAL regulates endothelial cell migration, proliferation, tube formation, permeability modulating ER-calcium homeostasis cytoskeleton dynamics. In zebrafish, taal modulation led defects, which were rescued human orthologue. Our studies further revealed that negatively Tie1 protein via ubiquitin-mediated degradation. Notably, expression upregulated in the blood DR patients downregulated models. Overexpression restored VE-cadherin surface expression. These findings establish regulator turnover, with potential implications diabetic retinopathy.

Язык: Английский

SCAR-6 elncRNA locus epigenetically regulates PROZ and modulates coagulation and vascular function DOI Creative Commons
Gyan Ranjan, Paras Sehgal, Vinod Scaria

и другие.

EMBO Reports, Год журнала: 2024, Номер unknown

Опубликована: Окт. 2, 2024

Abstract In this study, we characterize a novel lncRNA-producing gene locus that name Syntenic Cardiovascular Conserved Region-Associated lncRNA-6 (scar-6) and functionally validate its role in coagulation cardiovascular function. A 12-bp deletion of the scar-6 zebrafish ( gib007Δ12/Δ12 ) results cranial hemorrhage vascular permeability. Overexpression, knockdown rescue with lncRNA modulates hemostasis zebrafish. Molecular investigation reveals acts as an enhancer (elncRNA), controls expression prozb , inhibitor factor Xa through element locus. The suppresses loop formation between sequences, which might be facilitated by methylation CpG islands via prdm14-PRC2 complex whose binding to stabilized elncRNA transcript. Binding prdm14 is impaired Finally, activation PAR2 receptor triggers NF-κB -mediated endothelial cell activation, leading dysfunction hemorrhage. We present evidence plays regulating cascade maintains homeostasis.

Язык: Английский

Процитировано

1
SCAR-6 elncRNA locus epigenetically regulates PROZ and modulates coagulation and vascular function DOI
Gyan Ranjan, Paras Sehgal, Vinod Scaria

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Июль 22, 2024

Abstract Syntenic conservation is an effective strategy to identify evolutionarily conserved lncRNA orthologs. In this study, we identified a novel uncharacterized known as Cardiovascular Conserved Region-Associated lncRNA-6 (scar-6) and functionally validated its role in coagulation cardiovascular function. Precise editing of the scar-6 locus zebrafish ( gib007Δ12/Δ12 ) resulted cranial hemorrhage permeability defects. Further analysis, including overexpression, editing, rescue experiments, provided compelling evidence for critical transcript process zebrafish. Notably, attempts were unsuccessful mitigating hemorrhage. Molecular investigation revealed that RNA acts enhancer (elncRNA), controls expression prozb , inhibitor factor Xa through element on locus. The actively suppresses loop formation between sequences, facilitated by methylation CpG island via prdm14-PRC2 complex, which stabilized elncRNA transcript. Disruption mechanism led impaired vascular function subsequent This was triggered activation PAR2 receptor mediated upregulation turn caused NF-κB -mediated endothelial cell activation. study presents multifaceted locus, highlighting crucial regulating cascade gene maintaining homeostasis Synopsis ProZ-PZI natural activated X (F10) plays major hemostasis in-vivo. Here, evolutionary syntenic shown regulate control integrity (elncRNA). It modulates stabilizes Prdm14-PRC2 complex binding inhibits prozb/scar-6 looping methylating under wildtype conditions. Overexpressed edited animals activates receptor, causing dysfunction.

Язык: Английский

Процитировано

0
LncRNA TAAL is a Modulator of Tie1-Mediated Vascular Function in Diabetic Retinopathy DOI Creative Commons
Gyan Ranjan,

Samriddhi Arora,

Sarmeela Sharma

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Сен. 14, 2024

Diabetic retinopathy (DR), a leading cause of vision impairment and blindness, is characterized by abnormal retinal vascular changes due to chronic hyperglycemia. The Tie-1 signaling pathway, essential for growth remodeling, has emerged as key therapeutic target, though its molecular mechanisms interactome remain largely unclear. Through protein-centric approach, we identified novel lncRNA named it Tie1-associated angiogenic (TAAL). TAAL regulates endothelial cell migration, proliferation, tube formation, permeability modulating ER-calcium homeostasis cytoskeleton dynamics. In zebrafish, taal modulation led defects, which were rescued human orthologue. Our studies further revealed that negatively Tie1 protein via ubiquitin-mediated degradation. Notably, expression upregulated in the blood DR patients downregulated models. Overexpression restored VE-cadherin surface expression. These findings establish regulator turnover, with potential implications diabetic retinopathy.

Язык: Английский

Процитировано

0