title: Fibroblast growth factor receptor 1 is a key inhibitor of TGFβ signaling in the endothelium.
abstract: Abnormal vascular homeostasis can lead to increased proliferation of smooth muscle cells and deposition of extracellular matrix, resulting in neointima formation, which contributes to vascular lumen narrowing, a pathology that underlies diseases including transplant vasculopathy, the recurrence of stenosis, and atherosclerosis. Growth of neointima is in part due to endothelial-to-mesenchymal transition (EndMT), a transforming growth factor-β (TGFβ)-driven process, which leads to increased numbers of smooth muscle cells and fibroblasts and deposition of extracellular matrix. We reported that endothelial cell-specific knockout of fibroblast growth factor receptor 1 (FGFR1) led to activation of TGFβ signaling and development of EndMT in vitro and in vivo. Furthermore, EndMT in human diseased vasculature correlated with decreased abundance of FGFR1. These findings identify FGFR1 as the key regulator of TGFβ signaling and EndMT development.
authors.affiliation: Yale Cardiovascular Research Center, Section of Cardiovascular Medicine, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06520, USA. michael.simons@yale.edu pei-yu.chen@yale.edu.
authors.forename: Pei-Yu
authors.initials: PY
authors.lastname: Chen
authors.affiliation: Department of Surgery, Yale University School of Medicine, New Haven, CT 06520, USA.
authors.forename: Lingfeng
authors.initials: L
authors.lastname: Qin
authors.affiliation: Department of Surgery, Yale University School of Medicine, New Haven, CT 06520, USA.
authors.forename: George
authors.initials: G
authors.lastname: Tellides
authors.affiliation: Yale Cardiovascular Research Center, Section of Cardiovascular Medicine, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06520, USA. Department of Cell Biology, Yale University School of Medicine, New Haven, CT 06520, USA. michael.simons@yale.edu pei-yu.chen@yale.edu.
authors.forename: Michael
authors.initials: M
authors.lastname: Simons
mesh_terms: D000818:Animals; D054338:Cell Transdifferentiation; D003331:Coronary Vessels / Q000378:metabolism / Q000473:pathology / Q000637:transplantation; D004730:Endothelium, Vascular / Q000502:physiology*; D005109:Extracellular Matrix / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism / Q000473:pathology; D006084:Graft Rejection / Q000473:pathology; D016027:Heart Transplantation; D064593:Heterografts; D006614:Hindlimb / Q000098:blood supply; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D007511:Ischemia / Q000378:metabolism; D008648:Mesoderm / Q000166:cytology; D051379:Mice; D008817:Mice, Mutant Strains; D035683:MicroRNAs / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000473:pathology; D058426:Neointima / Q000503:physiopathology*; D051496:Receptor, Fibroblast Growth Factor, Type 1 / Q000172:deficiency / Q000502:physiology*; D017468:Receptors, Fibroblast Growth Factor / Q000037:antagonists & inhibitors; D015398:Signal Transduction / Q000502:physiology*; D051899:Smad2 Protein / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000502:physiology*; D018183:Transplantation Chimera
chemical_list: D035683:MicroRNAs; D017468:Receptors, Fibroblast Growth Factor; C497782:SMAD2 protein, human; D051899:Smad2 Protein; D016212:Transforming Growth Factor beta; C487931:mirnlet7 microRNA, human; C496348:FGFR1 protein, human; C496349:Fgfr1 protein, mouse; D051496:Receptor, Fibroblast Growth Factor, Type 1