@article{036465d598334d5dbfb38b4e0bceb47b,
title = "FGF2-induced STAT3 activation regulates pathologic neovascularization",
abstract = "Cell-autonomous endothelial cell (EC) fibroblast growth factor receptor (FGFR) signaling through FGFR1/2 is essential for injury-induced wound vascularization and pathologic neovascularization as in blinding eye diseases such as age-related macular degeneration. Which FGF ligand(s) is critical in regulating angiogenesis is unknown. Utilizing ex vivo models of choroidal endothelial sprouting and in vivo models of choroidal neovascularization (CNV), we demonstrate here that only FGF2 is the essential ligand. Though FGF-FGFR signaling can activate multiple intracellular signaling pathways, we show that FGF2 regulates pathogenic angiogenesis via STAT3 activation. The identification of FGF2 as a critical mediator in aberrant neovascularization provides a new opportunity for developing multi-target therapies in blinding eye diseases especially given the limitations of anti-VEGF monotherapy.",
keywords = "Choroid sprouting, Choroidal neovascularization, Endothelial cell, Fibroblast growth factor, Macular degeneration, Retina, STAT3",
author = "Zhenyu Dong and Andrea Santeford and Norimitsu Ban and Lee, {Tae Jun} and Craig Smith and Ornitz, {David M.} and Apte, {Rajendra S.}",
note = "Funding Information: This work was supported by NIH Grants R21 EY026707-01 (R.S.A. and D.M.O.), R01 EY019287-06 (R.S.A.), P30 EY02687 (Vision Core Grant); the Starr Foundation (R.S.A.); the Carl Marshall Reeves and Mildred Almen Reeves Foundation (R.S.A.); the Bill and Emily Kuzma Family Gift for Retinal Research (R.S.A.); a Physician Scientist Award and a Nelson Trust Award from Research to Prevent Blindness (R.S.A.); the Jeffrey Fort Innovation Fund (R.S.A.); the Glenn Foundation for Medical Research and the Thome Foundation (R.S.A.). Additional funding comes from an unrestricted grant to the Department of Ophthalmology and Visual Sciences of Washington University School of Medicine from Research to Prevent Blindness. Z.D. was supported by the VitreoRetinal Surgery Foundation . Funding Information: This work was supported by NIH Grants R21 EY026707-01 (R.S.A. and D.M.O.), R01 EY019287-06 (R.S.A.), P30 EY02687 (Vision Core Grant); the Starr Foundation (R.S.A.); the Carl Marshall Reeves and Mildred Almen Reeves Foundation (R.S.A.); the Bill and Emily Kuzma Family Gift for Retinal Research (R.S.A.); a Physician Scientist Award and a Nelson Trust Award from Research to Prevent Blindness (R.S.A.); the Jeffrey Fort Innovation Fund (R.S.A.); the Glenn Foundation for Medical Research and the Thome Foundation (R.S.A.). Additional funding comes from an unrestricted grant to the Department of Ophthalmology and Visual Sciences of Washington University School of Medicine from Research to Prevent Blindness. Z.D. was supported by the VitreoRetinal Surgery Foundation. Publisher Copyright: {\textcopyright} 2019 Elsevier Ltd",
year = "2019",
month = oct,
doi = "10.1016/j.exer.2019.107775",
language = "English",
volume = "187",
journal = "Experimental Eye Research",
issn = "0014-4835",
publisher = "Academic Press Inc.",
}