| Literature DB >> 28400392 |
Jonathan D Lam1, Daniel J Oh1, Lindsay L Wong1, Dhanesh Amarnani1, Cindy Park-Windhol1, Angie V Sanchez1, Jonathan Cardona-Velez1,2, Declan McGuone3, Anat O Stemmer-Rachamimov3, Dean Eliott4, Diane R Bielenberg5, Tave van Zyl4, Lishuang Shen6, Xiaowu Gai6, Patricia A D'Amore7,8, Leo A Kim7,4, Joseph F Arboleda-Velasquez7.
Abstract
Proliferative diabetic retinopathy (PDR) is a common cause of blindness in the developed world's working adult population and affects those with type 1 and type 2 diabetes. We identified Runt-related transcription factor 1 (RUNX1) as a gene upregulated in CD31+ vascular endothelial cells obtained from human PDR fibrovascular membranes (FVMs) via transcriptomic analysis. In vitro studies using human retinal microvascular endothelial cells (HRMECs) showed increased RUNX1 RNA and protein expression in response to high glucose, whereas RUNX1 inhibition reduced HRMEC migration, proliferation, and tube formation. Immunohistochemical staining for RUNX1 showed reactivity in vessels of patient-derived FVMs and angiogenic tufts in the retina of mice with oxygen-induced retinopathy, suggesting that RUNX1 upregulation is a hallmark of aberrant retinal angiogenesis. Inhibition of RUNX1 activity with the Ro5-3335 small molecule resulted in a significant reduction of neovascular tufts in oxygen-induced retinopathy, supporting the feasibility of targeting RUNX1 in aberrant retinal angiogenesis.Entities:
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Year: 2017 PMID： 28400392 PMCID： PMC5482092 DOI： 10.2337/db16-1035
Source DB: PubMed Journal: Diabetes ISSN： 0012-1797 Impact factor: 9.461