Journal article
Endothelial cell FGF signaling is required for injury response but not for vascular homeostasis
Proceedings of the National Academy of Sciences - PNAS, Vol.111(37), pp.13379-13384
09/16/2014
DOI: 10.1073/pnas.1324235111
PMCID: PMC4169958
PMID: 25139991
Abstract
Endothelial cells (ECs) express fibroblast growth factor receptors (FGFRs) and are exquisitely sensitive to FGF signals. However, whether the EC or another vascular cell type requires FGF signaling during development, homeostasis, and response to injury is not known. Here, we show that Flk1-Cre or Tie2-Cre mediated deletion of FGFR1 and FGFR2 (Fgfr1/2(Flk1-Cre) or Fgfr1/2(Tie2-Cre) mice), which results in deletion in endothelial and hematopoietic cells, is compatible with normal embryonic development. As adults, Fgfr1/2(Flk1-Cre) mice maintain normal blood pressure and vascular reactivity and integrity under homeostatic conditions. However, neovascularization after skin or eye injury was significantly impaired in both Fgfr1/2(Flk1-Cre) and Fgfr1/2(Tie2-Cre) mice, independent of either hematopoietic cell loss of FGFR1/2 or vascular endothelial growth factor receptor 2 (Vegfr2) haploinsufficiency. Also, impaired neovascularization was associated with delayed cutaneous wound healing. These findings reveal a key requirement for cell-autonomous EC FGFR signaling in injury-induced angiogenesis, but not for vascular homeostasis, identifying the EC FGFR signaling pathway as a target for diseases associated with aberrant vascular proliferation, such as age-related macular degeneration, and for modulating wound healing without the potential toxicity associated with direct manipulation of systemic FGF or VEGF activity.
Details
- Title: Subtitle
- Endothelial cell FGF signaling is required for injury response but not for vascular homeostasis
- Creators
- Sunday S Oladipupo - Departments of Developmental BiologyCraig Smith - Departments of Developmental BiologyAndrea Santeford - Ophthalmology and Visual SciencesChangwon Park - Washington University in St. LouisAbdoulaye Sene - Ophthalmology and Visual SciencesLuke A Wiley - Ophthalmology and Visual SciencesPatrick Osei-Owusu - Cell Biology and Physiology, andJoann Hsu - Departments of Developmental BiologyNicole Zapata - Ophthalmology and Visual SciencesFang Liu - Pathology and ImmunologyRei Nakamura - Ophthalmology and Visual SciencesKory J Lavine - Departments of Developmental Biology, Medicine, Washington University School of Medicine, St. Louis, MO 63110Kendall J Blumer - Cell Biology and Physiology, andKyunghee Choi - Washington University in St. LouisRajendra S Apte - Departments of Developmental Biology, Ophthalmology and Visual Sciences, apte@vision.wustl.edu dornitz@wustl.eduDavid M Ornitz - Departments of Developmental Biology, apte@vision.wustl.edu dornitz@wustl.edu
- Resource Type
- Journal article
- Publication Details
- Proceedings of the National Academy of Sciences - PNAS, Vol.111(37), pp.13379-13384
- Publisher
- United States
- DOI
- 10.1073/pnas.1324235111
- PMID
- 25139991
- PMCID
- PMC4169958
- ISSN
- 0027-8424
- eISSN
- 1091-6490
- Grant note
- R01 GM044592 / NIGMS NIH HHS HL105732 / NHLBI NIH HHS R29 HL055337 / NHLBI NIH HHS P30EY02687 / NEI NIH HHS T32 HL007275 / NHLBI NIH HHS HL55337 / NHLBI NIH HHS R01 HL105732 / NHLBI NIH HHS R01 HL063736 / NHLBI NIH HHS EY019287 / NEI NIH HHS P30 EY002687 / NEI NIH HHS P30 AR057235 / NIAMS NIH HHS R01 EY019287 / NEI NIH HHS R01 HL055337 / NHLBI NIH HHS K08 HL123519 / NHLBI NIH HHS HL63736 / NHLBI NIH HHS P30 DK052574 / NIDDK NIH HHS
- Language
- English
- Date published
- 09/16/2014
- Academic Unit
- Ophthalmology and Visual Sciences
- Record Identifier
- 9983980073402771
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