Table 1.
FGF signaling pathway components active in vascular cells
| Gene | Vascular expression | Vascular activity/functions | Mutant mouse phenotypes |
|---|---|---|---|
| FGF1 | EC, VSMC [2] | Mitogen, chemotactic for EC, VSMC [3, 34] | Fgf1−/− mice show normal development and viability [36] |
| FGF2 | EC, VSMC [2] | Mitogen, chemotactic for EC, VSMC [3, 34] | Fgf2−/− mice have mild phenotype in vascular tone [37], delayed wound healing [38] |
| FGF5 | EC, VSMC [2] | Arteriogenic [39] | Abnormally long hair in Fgf5−/− mice [40] |
| FGF7 | EC, VSMC [2] | EC migration [41] | Defects in hair development in Fgf7−/− mice [42] |
| FGF8 | EC, SMC [2] | Cardiovascular morphogenesis [43] | Fgf8−/− mice have outflow tract defects, defects in VSMC of large vessels [43] |
| FGF16 | EC, VSMC [2] | Promotes EC migration [44] | Fgf16−/− mice have defects in cardiac morphogenesis [45] |
| FGF18 | EC, VSMC [2] | Promotes EC migration [44] | Fgf18−/− mice show postnatal lethal, defects in osteogenesis and chondrogenesis [46], and the lung [47] |
| FGFR1 (FGFR1IIIc) | EC, VSMC [2] | Activates MAPK and Akt pathways in EC and VSMC [3, 14] | Fgfr1−/− mice are embryonic lethal [48], compound deletion of Fgfr1/Fgfr2 in ECs results in defects in wound healing [49••] |
| FGFR2 (FGFR2IIIc) | EC, VSMC [2] | Activates MAPK and Akt pathways in EC and VSMC [3, 14] | Fgfr2−/− mice are embryonic lethal [50], compound deletion of Fgfr1/Fgfr2 in ECs results in defects in wound healing [49••] |
| FGFR3 (FGFR3IIIc) | EC, VSMC [2] | Activates MAPK and Akt pathways in EC and VSMC [3, 14] | Defects in skeleton and hearing in Fgfr3−/− mice [51] |
| FGFR5 (FGFRL1) | EC [2] | Unknown | Defects in kidney development of Fgfrl1−/− mice [52] |
| Klotho | EC, VSMC [53••] | Prevents vascular calcification [53••] | Premature aging, vascular calcification in Kl−/− mice [54] |
| Syndecan-4 | EC, VSMC [7] | Transmembrane protein that binds FGFs to propagate signals via FGFR1, involved in FGFR endocytosis [7] | Sdc4−/− mice have decreased neointimal lesion formation in injured vasculature [55], increased mortality after myocardial infarction [56] |
| Spry1 | EC, VSMC [2] | Inhibits EC proliferation and tubulogenesis [57, 58], promotes VSMC contractile phenotype [59] | Defects in kidney development [60]; gain of function mutants embryonic lethal with hematopoietic and vascular defects [61] |
| Spry2 | EC, VSMC [2] | Inhibits EC and VSMC proliferation [57] | Spry2/Spry4 double mutants lethal at E12.5 with vascular defects [62] |
| Spry3 | EC, VSMC [2] | Unknown | Unknown |
| Spry4 | EC, VSMC [2] | Inhibits migration and adhesion of EC [63] | Viable with increased vascular density, resistant to hindlimb ischemia due to accelerated neovascularization [64] |
| Sef (IL17RD) | EC, VSMC [2] | Binds and inhibits FGFR1 kinase activity [65] | Postnatal cortical bone thickening [66], not yet tested in adult pathology |
Listed are components of the FGF signaling pathway that are found in endothelial cells or smooth muscle cells, and their vascular-related functions and mouse model phenotypes