{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T09:50:17Z","timestamp":1791453017003,"version":"4.3.3"},"reference-count":104,"publisher":"Ovid Technologies (Wolters Kluwer Health)","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["ATVB"],"abstract":"<jats:sec>\n                    <jats:title>BACKGROUND:<\/jats:title>\n                    <jats:p>TIE1 is an endothelial receptor tyrosine kinase, which plays a crucial role in vascular development and remodeling, including in diseases such as diabetic retinopathy (DR). However, the molecular mechanisms and regulatory interactome governing TIE1 function remain largely unknown. Long noncoding RNAs (lncRNAs) are increasingly recognized as key regulators of endothelial gene expression and vascular homeostasis, yet lncRNA regulators of TIE1 have not been characterized. This study was designed to identify lncRNA regulators of TIE1 and elucidate their functional roles in endothelial biology and DR pathogenesis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS:<\/jats:title>\n                    <jats:p>Using a protein-centric RNA immunoprecipitation sequencing approach in human umbilical vein endothelial cell\/Tert2 cells, we identified a novel TIE1-interacting lncRNA. Functional characterization was performed via siRNA-mediated knockdown and plasmid-based overexpression, followed by assays for migration, proliferation, tube formation, permeability, calcium imaging, and cytoskeletal dynamics. Protein turnover was assessed by cycloheximide chase, proteasomal\/lysosomal inhibition, and ubiquitin pulldown. Functional conservation was evaluated in zebrafish through morpholino knockdown and human-orthologue complementation. Clinical relevance was investigated in cadaveric retinal tissues (n=17 controls; n=14 diabetic) and peripheral blood samples from controls (n=60), diabetic without retinopathy (n=50), nonproliferative DR (n=70), and proliferative DR (n=50) participants, alongside a hyperglycemic zebrafish DR model.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS:<\/jats:title>\n                    <jats:p>\n                      We identified\n                      <jats:italic toggle=\"yes\">TAAL<\/jats:italic>\n                      , which specifically interacts with TIE1 but not TIE2.\n                      <jats:italic toggle=\"yes\">TAAL<\/jats:italic>\n                      regulated endothelial migration, proliferation, tube formation, and permeability by maintaining endoplasmic reticulum\u2013calcium homeostasis and cytoskeletal dynamics. Mechanistically,\n                      <jats:italic toggle=\"yes\">TAAL<\/jats:italic>\n                      negatively regulated TIE1 protein levels via ubiquitin-mediated degradation without altering\n                      <jats:italic toggle=\"yes\">TIE1<\/jats:italic>\n                      mRNA expression. Its function was conserved in zebrafish, where\n                      <jats:italic toggle=\"yes\">taal<\/jats:italic>\n                      knockdown produced angiogenic defects rescued by human\n                      <jats:italic toggle=\"yes\">TAAL<\/jats:italic>\n                      . Under hyperglycemia,\n                      <jats:italic toggle=\"yes\">TAAL<\/jats:italic>\n                      was downregulated in endothelial cells but upregulated in mixed retinal cultures, diabetic retinal tissues, and nonproliferative DR\/proliferative DR patient blood, supporting biomarker potential.\n                      <jats:italic toggle=\"yes\">TAAL<\/jats:italic>\n                      overexpression restored endothelial barrier integrity and VE-cadherin (vascular endothelial cadherin) localization in vitro and prevented vascular leakage in vivo in zebrafish.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSIONS:<\/jats:title>\n                    <jats:p>\n                      <jats:italic toggle=\"yes\">TAAL<\/jats:italic>\n                      regulates TIE1 protein turnover through ubiquitination and calcium-mediated vascular remodeling, exhibiting cell type\u2013specific regulation under diabetic stress, positioning it as both a minimally invasive biomarker and therapeutic target for DR.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/atvbaha.126.324094","type":"journal-article","created":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T09:00:47Z","timestamp":1791450047000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":0,"title":["LncRNA\n                    <i>TAAL<\/i>\n                    Regulates TIE1-Mediated Vascular Remodeling and Is Associated With Diabetic Retinopathy"],"prefix":"10.1161","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3161-4796","authenticated-orcid":true,"given":"Gyan","family":"Ranjan","sequence":"first","affiliation":[{"name":"Laboratory of Calciomics and Systemic Pathophysiology, Regional Center for Biotechnology (RCB), Faridabad, India (G.R., S.A., R.K.M.)."},{"name":"CSIR Institute of Genomics and Integrative Biology, New Delhi, India (G.R., R.C.B., V. Senthivel, V. Scaria, S. Sivasubbu)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samriddhi","family":"Arora","sequence":"additional","affiliation":[{"name":"Laboratory of Calciomics and Systemic Pathophysiology, Regional Center for Biotechnology (RCB), Faridabad, India (G.R., S.A., R.K.M.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarmeela","family":"Sharma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rahul C.","family":"Bhoyar","sequence":"additional","affiliation":[{"name":"CSIR Institute of Genomics and Integrative Biology, New Delhi, India (G.R., R.C.B., V. Senthivel, V. Scaria, S. Sivasubbu)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0378-7593","authenticated-orcid":true,"given":"Vigneshwar","family":"Senthivel","sequence":"additional","affiliation":[{"name":"CSIR Institute of Genomics and Integrative Biology, New Delhi, India (G.R., R.C.B., V. Senthivel, V. Scaria, S. Sivasubbu)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0192-0178","authenticated-orcid":true,"given":"Ritesh","family":"Narula","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7644-7181","authenticated-orcid":true,"given":"Vinod","family":"Scaria","sequence":"additional","affiliation":[{"name":"CSIR Institute of Genomics and Integrative Biology, New Delhi, India (G.R., R.C.B., V. Senthivel, V. Scaria, S. Sivasubbu)."},{"name":"Karkinos Healthcare Pvt. Ltd, Navi Mumbai, India (V. Scaria, S. Sivasubbu)."},{"name":"Dr. D.Y Patil Medical College, Hospital and Research Centre, Pune, India (V. Scaria, S. Sivasubbu)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3717-4963","authenticated-orcid":true,"given":"Subhabrata","family":"Chakrabarti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3660-5039","authenticated-orcid":true,"given":"Inderjeet","family":"Kaur","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sridhar","family":"Sivasubbu","sequence":"additional","affiliation":[{"name":"CSIR Institute of Genomics and Integrative Biology, New Delhi, India (G.R., R.C.B., V. Senthivel, V. Scaria, S. Sivasubbu)."},{"name":"Karkinos Healthcare Pvt. Ltd, Navi Mumbai, India (V. Scaria, S. Sivasubbu)."},{"name":"Dr. D.Y Patil Medical College, Hospital and Research Centre, Pune, India (V. Scaria, S. 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