Journal article
Endothelial cell FGF signaling is required for injury response but not for vascular homeostasis
Proceedings of the National Academy of Sciences - PNAS, v 111(37), pp 13379-13384
16 Sep 2014
PMID: 25139991
Featured in Collection : UN Sustainable Development Goals @ Drexel
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.
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Details
- Title
- Endothelial cell FGF signaling is required for injury response but not for vascular homeostasis
- Creators
- Sunday S Oladipupo - Departments of Developmental Biology.Craig Smith - Departments of Developmental Biology.Andrea Santeford - Visual SciencesChangwon Park - Pathology and Immunology.Abdoulaye Sene - Visual SciencesLuke A Wiley - Visual SciencesPatrick Osei-Owusu - Cell Biology and Physiology, and.Joann Hsu - Departments of Developmental Biology.Nicole Zapata - Visual SciencesFang Liu - Pathology and Immunology.Rei Nakamura - Visual SciencesKory J Lavine - Washington University in St. LouisKendall J Blumer - Cell Biology and Physiology, and.Kyunghee Choi - Pathology and Immunology.Rajendra S Apte - Visual SciencesDavid M Ornitz - Departments of Developmental Biology.Clara Park - Drexel Solutions Institute (2018-)
- Publication Details
- Proceedings of the National Academy of Sciences - PNAS, v 111(37), pp 13379-13384
- Publisher
- PNAS
- 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
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Drexel Solutions Institute; Pharmacology and Physiology
- Web of Science ID
- WOS:000341630000042
- Scopus ID
- 2-s2.0-84907215716
- Other Identifier
- 991019173530604721
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