@article {1549026,
	title = {TNF-α signaling regulates RUNX1 function in endothelial cells},
	journal = {FASEB J},
	volume = {35},
	number = {2},
	year = {2021},
	month = {2021 Feb},
	pages = {e21155},
	abstract = {Runt-related transcription factor 1 (RUNX1) acts as a mediator of aberrant retinal angiogenesis and has been implicated in the progression of proliferative diabetic retinopathy (PDR). Patients with PDR, retinopathy of prematurity (ROP), and wet age-related macular degeneration (wet AMD) have been found to have elevated levels of Tumor Necrosis Factor-alpha (TNF-α) in the eye. In fibrovascular membranes (FVMs) taken from patients with PDR RUNX1 expression was increased in the vasculature, while in human retinal microvascular endothelial cells (HRMECs), TNF-α stimulation causes increased RUNX1 expression, which can be modulated by RUNX1 inhibitors. Using TNF-α pathway inhibitors, we determined that in HRMECs, TNF-α-induced RUNX1 expression occurs via JNK activation, while NF-κB and p38/MAPK inhibition did not affect RUNX1 expression. JNK inhibitors were also effective at stopping high D-glucose-stimulated RUNX1 expression. We further linked JNK to RUNX1 through Activator Protein 1 (AP-1) and investigated the JNK-AP-1-RUNX1 regulatory feedback loop, which can be modulated by VEGF. Additionally, stimulation with TNF-α and D-glucose had an additive effect on RUNX1 expression, which was downregulated by VEGF modulation. These data suggest that the downregulation of RUNX1 in conjunction with anti-VEGF agents may be important in future treatments for the management of diseases of pathologic ocular angiogenesis.},
	issn = {1530-6860},
	doi = {10.1096/fj.202001668R},
	author = {Whitmore, Hannah A B and Amarnani, Dhanesh and O{\textquoteright}Hare, Michael and Delgado-Tirado, Santiago and Gonzalez-Buendia, Lucia and An, Miranda and Pedron, Julien and Bushweller, John H and Arboleda-Velasquez, Joseph F and Kim, Leo A}
}
