Foxc1 and Foxc2 deletion causes abnormal lymphangiogenesis and correlates with ERK hyperactivation
Identifieur interne : 012F85 ( Main/Exploration ); précédent : 012F84; suivant : 012F86Foxc1 and Foxc2 deletion causes abnormal lymphangiogenesis and correlates with ERK hyperactivation
Auteurs : Anees Fatima [États-Unis] ; Ying Wang [États-Unis] ; Yutaka Uchida [États-Unis] ; Pieter Norden [États-Unis] ; Ting Liu [États-Unis] ; Austin Culver [États-Unis] ; William H. Dietz [États-Unis] ; Ford Culver [États-Unis] ; Meredith Millay [États-Unis] ; Yoh-Suke Mukouyama [États-Unis] ; Tsutomu Kume [États-Unis]Source :
- The Journal of Clinical Investigation [ 0021-9738 ] ; ????.
Abstract
The lymphatic vasculature is essential for maintaining interstitial fluid homeostasis, and dysfunctional lymphangiogenesis contributes to various pathological processes, including inflammatory disease and tumor metastasis. Mutations in
Url:
DOI: 10.1172/JCI80465
PubMed: 27214551
PubMed Central: 4922698
Affiliations:
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Mukouyama</name><affiliation wicri:level="2"><nlm:aff id="A3">Laboratory of Stem Cell and Neuro-Vascular Biology, Genetics and Developmental Biology Center, National Heart, Lung, and Blood Institute, NIH, Bethesda, Maryland, USA.</nlm:aff><country xml:lang="fr" wicri:curation="lc">États-Unis</country><wicri:regionArea>Laboratory of Stem Cell and Neuro-Vascular Biology, Genetics and Developmental Biology Center, National Heart, Lung, and Blood Institute, NIH, Bethesda, Maryland</wicri:regionArea><placeName><region type="state">Maryland</region></placeName></affiliation></author><author><name sortKey="Kume, Tsutomu" sort="Kume, Tsutomu" uniqKey="Kume T" first="Tsutomu" last="Kume">Tsutomu Kume</name><affiliation wicri:level="2"><nlm:aff id="A1">Feinberg Cardiovascular Research Institute, Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA.</nlm:aff><country xml:lang="fr" wicri:curation="lc">États-Unis</country><wicri:regionArea>Feinberg 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hyperactivation</title><author><name sortKey="Fatima, Anees" sort="Fatima, Anees" uniqKey="Fatima A" first="Anees" last="Fatima">Anees Fatima</name><affiliation wicri:level="2"><nlm:aff id="A1">Feinberg Cardiovascular Research Institute, Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA.</nlm:aff><country xml:lang="fr" wicri:curation="lc">États-Unis</country><wicri:regionArea>Feinberg Cardiovascular Research Institute, Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, Illinois</wicri:regionArea><placeName><region type="state">Illinois</region></placeName></affiliation></author><author><name sortKey="Wang, Ying" sort="Wang, Ying" uniqKey="Wang Y" first="Ying" last="Wang">Ying Wang</name><affiliation wicri:level="2"><nlm:aff id="A2">Department of Biochemistry and Molecular Biology, College of Medicine, Mayo Clinic, Rochester, Minnesota, USA.</nlm:aff><country xml:lang="fr" wicri:curation="lc">États-Unis</country><wicri:regionArea>Department of Biochemistry and Molecular Biology, College of Medicine, Mayo Clinic, Rochester, Minnesota</wicri:regionArea><placeName><region type="state">Minnesota</region></placeName></affiliation></author><author><name sortKey="Uchida, Yutaka" sort="Uchida, Yutaka" uniqKey="Uchida Y" first="Yutaka" last="Uchida">Yutaka Uchida</name><affiliation wicri:level="2"><nlm:aff id="A3">Laboratory of Stem Cell and Neuro-Vascular Biology, Genetics and Developmental Biology Center, National Heart, Lung, and Blood Institute, NIH, Bethesda, Maryland, USA.</nlm:aff><country xml:lang="fr" wicri:curation="lc">États-Unis</country><wicri:regionArea>Laboratory of Stem Cell and Neuro-Vascular Biology, Genetics and Developmental Biology Center, National Heart, Lung, and Blood Institute, NIH, Bethesda, Maryland</wicri:regionArea><placeName><region type="state">Maryland</region></placeName></affiliation></author><author><name sortKey="Norden, Pieter" sort="Norden, Pieter" uniqKey="Norden P" first="Pieter" last="Norden">Pieter Norden</name><affiliation wicri:level="2"><nlm:aff id="A1">Feinberg Cardiovascular Research Institute, Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA.</nlm:aff><country xml:lang="fr" wicri:curation="lc">États-Unis</country><wicri:regionArea>Feinberg Cardiovascular Research Institute, Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, Illinois</wicri:regionArea><placeName><region type="state">Illinois</region></placeName></affiliation></author><author><name sortKey="Liu, Ting" sort="Liu, Ting" uniqKey="Liu T" first="Ting" last="Liu">Ting Liu</name><affiliation wicri:level="2"><nlm:aff id="A1">Feinberg Cardiovascular Research Institute, Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA.</nlm:aff><country xml:lang="fr" wicri:curation="lc">États-Unis</country><wicri:regionArea>Feinberg Cardiovascular Research Institute, Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, Illinois</wicri:regionArea><placeName><region type="state">Illinois</region></placeName></affiliation></author><author><name sortKey="Culver, Austin" sort="Culver, Austin" uniqKey="Culver A" first="Austin" last="Culver">Austin Culver</name><affiliation wicri:level="2"><nlm:aff id="A1">Feinberg Cardiovascular Research Institute, Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA.</nlm:aff><country xml:lang="fr" wicri:curation="lc">États-Unis</country><wicri:regionArea>Feinberg Cardiovascular Research Institute, Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, Illinois</wicri:regionArea><placeName><region type="state">Illinois</region></placeName></affiliation></author><author><name sortKey="Dietz, William H" sort="Dietz, William H" uniqKey="Dietz W" first="William H." last="Dietz">William H. Dietz</name><affiliation wicri:level="2"><nlm:aff id="A1">Feinberg Cardiovascular Research Institute, Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA.</nlm:aff><country xml:lang="fr" wicri:curation="lc">États-Unis</country><wicri:regionArea>Feinberg Cardiovascular Research Institute, Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, Illinois</wicri:regionArea><placeName><region type="state">Illinois</region></placeName></affiliation></author><author><name sortKey="Culver, Ford" sort="Culver, Ford" uniqKey="Culver F" first="Ford" last="Culver">Ford Culver</name><affiliation wicri:level="2"><nlm:aff id="A1">Feinberg Cardiovascular Research Institute, Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA.</nlm:aff><country xml:lang="fr" wicri:curation="lc">États-Unis</country><wicri:regionArea>Feinberg Cardiovascular Research Institute, Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, Illinois</wicri:regionArea><placeName><region type="state">Illinois</region></placeName></affiliation></author><author><name sortKey="Millay, Meredith" sort="Millay, Meredith" uniqKey="Millay M" first="Meredith" last="Millay">Meredith Millay</name><affiliation wicri:level="2"><nlm:aff id="A1">Feinberg Cardiovascular Research Institute, Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA.</nlm:aff><country xml:lang="fr" wicri:curation="lc">États-Unis</country><wicri:regionArea>Feinberg Cardiovascular Research Institute, Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, Illinois</wicri:regionArea><placeName><region type="state">Illinois</region></placeName></affiliation></author><author><name sortKey="Mukouyama, Yoh Suke" sort="Mukouyama, Yoh Suke" uniqKey="Mukouyama Y" first="Yoh-Suke" last="Mukouyama">Yoh-Suke Mukouyama</name><affiliation wicri:level="2"><nlm:aff id="A3">Laboratory of Stem Cell and Neuro-Vascular Biology, Genetics and Developmental Biology Center, National Heart, Lung, and Blood Institute, NIH, Bethesda, Maryland, USA.</nlm:aff><country xml:lang="fr" wicri:curation="lc">États-Unis</country><wicri:regionArea>Laboratory of Stem Cell and Neuro-Vascular Biology, Genetics and Developmental Biology Center, National Heart, Lung, and Blood Institute, NIH, Bethesda, Maryland</wicri:regionArea><placeName><region type="state">Maryland</region></placeName></affiliation></author><author><name sortKey="Kume, Tsutomu" sort="Kume, Tsutomu" uniqKey="Kume T" first="Tsutomu" last="Kume">Tsutomu Kume</name><affiliation wicri:level="2"><nlm:aff id="A1">Feinberg Cardiovascular Research Institute, Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA.</nlm:aff><country xml:lang="fr" wicri:curation="lc">États-Unis</country><wicri:regionArea>Feinberg Cardiovascular Research Institute, Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, Illinois</wicri:regionArea><placeName><region type="state">Illinois</region></placeName></affiliation></author></analytic><series><title level="j">The Journal of Clinical Investigation</title><idno type="ISSN">0021-9738</idno><idno type="eISSN">1558-8238</idno><imprint><date when="????">????</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>The lymphatic vasculature is essential for maintaining interstitial fluid homeostasis, and dysfunctional lymphangiogenesis contributes to various pathological processes, including inflammatory disease and tumor metastasis. Mutations in <italic>FOXC2</italic> are dominantly associated with late-onset lymphedema; however, the precise role of FOXC2 and a closely related factor, FOXC1, in the lymphatic system remains largely unknown. Here we identified a molecular cascade by which FOXC1 and FOXC2 regulate ERK signaling in lymphatic vessel growth. In mice, lymphatic endothelial cell–specific (LEC-specific) deletion of <italic>Foxc1</italic>, <italic>Foxc2</italic>, or both resulted in increased LEC proliferation, enlarged lymphatic vessels, and abnormal lymphatic vessel morphogenesis. Compared with LECs from control animals, LECs from mice lacking both <italic>Foxc1</italic> and <italic>Foxc2</italic> exhibited aberrant expression of Ras regulators, and embryos with LEC-specific deletion of <italic>Foxc1</italic> and <italic>Foxc2</italic>, alone or in combination, exhibited ERK hyperactivation. Pharmacological ERK inhibition in utero abolished the abnormally enlarged lymphatic vessels in FOXC-deficient embryos. Together, these results identify FOXC1 and FOXC2 as essential regulators of lymphangiogenesis and indicate a new potential mechanistic basis for lymphatic-associated diseases.</p></div></front></TEI><affiliations><list><country><li>États-Unis</li></country><region><li>Illinois</li><li>Maryland</li><li>Minnesota</li></region></list><tree><country name="États-Unis"><region name="Illinois"><name sortKey="Fatima, Anees" sort="Fatima, Anees" uniqKey="Fatima A" first="Anees" last="Fatima">Anees Fatima</name></region><name sortKey="Culver, Austin" sort="Culver, Austin" uniqKey="Culver A" first="Austin" last="Culver">Austin Culver</name><name sortKey="Culver, Ford" sort="Culver, Ford" uniqKey="Culver F" first="Ford" last="Culver">Ford Culver</name><name sortKey="Dietz, William H" sort="Dietz, William H" uniqKey="Dietz W" first="William H." last="Dietz">William H. Dietz</name><name sortKey="Kume, Tsutomu" sort="Kume, Tsutomu" uniqKey="Kume T" first="Tsutomu" last="Kume">Tsutomu Kume</name><name sortKey="Liu, Ting" sort="Liu, Ting" uniqKey="Liu T" first="Ting" last="Liu">Ting Liu</name><name sortKey="Millay, Meredith" sort="Millay, Meredith" uniqKey="Millay M" first="Meredith" last="Millay">Meredith Millay</name><name sortKey="Mukouyama, Yoh Suke" sort="Mukouyama, Yoh Suke" uniqKey="Mukouyama Y" first="Yoh-Suke" last="Mukouyama">Yoh-Suke Mukouyama</name><name sortKey="Norden, Pieter" sort="Norden, Pieter" uniqKey="Norden P" first="Pieter" last="Norden">Pieter Norden</name><name sortKey="Uchida, Yutaka" sort="Uchida, Yutaka" uniqKey="Uchida Y" first="Yutaka" last="Uchida">Yutaka Uchida</name><name sortKey="Wang, Ying" sort="Wang, Ying" uniqKey="Wang Y" first="Ying" last="Wang">Ying Wang</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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