FOXC2 controls Ang-2 expression and modulates angiogenesis, vascular patterning, remodeling, and functions in adipose tissue
Identifieur interne : 003161 ( Pmc/Corpus ); précédent : 003160; suivant : 003162FOXC2 controls Ang-2 expression and modulates angiogenesis, vascular patterning, remodeling, and functions in adipose tissue
Auteurs : Yuan Xue ; Renhai Cao ; Daniel Nilsson ; Shaohua Chen ; Rickard Westergren ; Eva-Maria Hedlund ; Cecile Martijn ; Lena Rondahl ; Per Krauli ; Erik Walum ; Sven Enerb Ck ; Yihai CaoSource :
- Proceedings of the National Academy of Sciences of the United States of America [ 0027-8424 ] ; 2008.
Abstract
Adipogenesis is spatiotemporally coupled to angiogenesis throughout adult life, and the interplay between these two processes is communicated by multiple factors. Here we show that in a transgenic mouse model, increased expression of forkhead box C2 (FOXC2) in the adipose tissue affects angiogenesis, vascular patterning, and functions. White and brown adipose tissues contain a considerably high density of microvessels appearing as vascular plexuses, which show redistribution of vascular smooth muscle cells and pericytes. Dysfunction of these primitive vessels is reflected by impairment of skin wound healing. We further provide a mechanistic insight of the vascular phenotype by showing that FOXC2 controls Ang-2 expression by direct activation of its promoter in adipocytes. Remarkably, an Ang-2-specific antagonist almost completely reverses this vascular phenotype. Thus, the FOXC2–Ang-2 signaling system is crucial for controlling adipose vascular function, which is part of an adaptation to increased adipose tissue metabolism.
Url:
DOI: 10.1073/pnas.0802486105
PubMed: 18621714
PubMed Central: 2481379
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PMC:2481379Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">FOXC2 controls Ang-2 expression and modulates angiogenesis, vascular patterning, remodeling, and functions in adipose tissue</title><author><name sortKey="Xue, Yuan" sort="Xue, Yuan" uniqKey="Xue Y" first="Yuan" last="Xue">Yuan Xue</name><affiliation><nlm:aff id="aff1">*Laboratory of Angiogenesis Research, Department of Microbiology, Tumor and Cell Biology, Karolinska Institute, 171 77 Stockholm, Sweden;</nlm:aff></affiliation></author><author><name sortKey="Cao, Renhai" sort="Cao, Renhai" uniqKey="Cao R" first="Renhai" last="Cao">Renhai Cao</name><affiliation><nlm:aff id="aff1">*Laboratory of Angiogenesis Research, Department of Microbiology, Tumor and Cell Biology, Karolinska Institute, 171 77 Stockholm, Sweden;</nlm:aff></affiliation></author><author><name sortKey="Nilsson, Daniel" sort="Nilsson, Daniel" uniqKey="Nilsson D" first="Daniel" last="Nilsson">Daniel Nilsson</name><affiliation><nlm:aff wicri:cut="; and" id="aff2">Department of Medical and Clinical Genetics, Institute of Biomedicine, the Sahlgrenska Academy, Göteborg University, Box 440, SE 405 30 Göteborg, Sweden</nlm:aff></affiliation></author><author><name sortKey="Chen, Shaohua" sort="Chen, Shaohua" uniqKey="Chen S" first="Shaohua" last="Chen">Shaohua Chen</name><affiliation><nlm:aff id="aff1">*Laboratory of Angiogenesis Research, Department of Microbiology, Tumor and Cell Biology, Karolinska Institute, 171 77 Stockholm, Sweden;</nlm:aff></affiliation></author><author><name sortKey="Westergren, Rickard" sort="Westergren, Rickard" uniqKey="Westergren R" first="Rickard" last="Westergren">Rickard Westergren</name><affiliation><nlm:aff wicri:cut="; and" id="aff2">Department of Medical and Clinical Genetics, Institute of Biomedicine, the Sahlgrenska Academy, Göteborg University, Box 440, SE 405 30 Göteborg, Sweden</nlm:aff></affiliation></author><author><name sortKey="Hedlund, Eva Maria" sort="Hedlund, Eva Maria" uniqKey="Hedlund E" first="Eva-Maria" last="Hedlund">Eva-Maria Hedlund</name><affiliation><nlm:aff id="aff1">*Laboratory of Angiogenesis Research, Department of Microbiology, Tumor and Cell Biology, Karolinska Institute, 171 77 Stockholm, Sweden;</nlm:aff></affiliation></author><author><name sortKey="Martijn, Cecile" sort="Martijn, Cecile" uniqKey="Martijn C" first="Cecile" last="Martijn">Cecile Martijn</name><affiliation><nlm:aff id="aff3">Biovitrum AB, Strandbergsgatan 49, P12-4, SE-112 76 Stockholm, Sweden</nlm:aff></affiliation></author><author><name sortKey="Rondahl, Lena" sort="Rondahl, Lena" uniqKey="Rondahl L" first="Lena" last="Rondahl">Lena Rondahl</name><affiliation><nlm:aff id="aff3">Biovitrum AB, Strandbergsgatan 49, P12-4, SE-112 76 Stockholm, Sweden</nlm:aff></affiliation></author><author><name sortKey="Krauli, Per" sort="Krauli, Per" uniqKey="Krauli P" first="Per" last="Krauli">Per Krauli</name><affiliation><nlm:aff id="aff3">Biovitrum AB, Strandbergsgatan 49, P12-4, SE-112 76 Stockholm, Sweden</nlm:aff></affiliation></author><author><name sortKey="Walum, Erik" sort="Walum, Erik" uniqKey="Walum E" first="Erik" last="Walum">Erik Walum</name><affiliation><nlm:aff id="aff3">Biovitrum AB, Strandbergsgatan 49, P12-4, SE-112 76 Stockholm, Sweden</nlm:aff></affiliation></author><author><name sortKey="Enerb Ck, Sven" sort="Enerb Ck, Sven" uniqKey="Enerb Ck S" first="Sven" last="Enerb Ck">Sven Enerb Ck</name><affiliation><nlm:aff wicri:cut="; and" id="aff2">Department of Medical and Clinical Genetics, Institute of Biomedicine, the Sahlgrenska Academy, Göteborg University, Box 440, SE 405 30 Göteborg, Sweden</nlm:aff></affiliation></author><author><name sortKey="Cao, Yihai" sort="Cao, Yihai" uniqKey="Cao Y" first="Yihai" last="Cao">Yihai Cao</name><affiliation><nlm:aff id="aff1">*Laboratory of Angiogenesis Research, Department of Microbiology, Tumor and Cell Biology, Karolinska Institute, 171 77 Stockholm, Sweden;</nlm:aff></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">18621714</idno><idno type="pmc">2481379</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2481379</idno><idno type="RBID">PMC:2481379</idno><idno type="doi">10.1073/pnas.0802486105</idno><date when="2008">2008</date><idno type="wicri:Area/Pmc/Corpus">003161</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">003161</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">FOXC2 controls Ang-2 expression and modulates angiogenesis, vascular patterning, remodeling, and functions in adipose tissue</title><author><name sortKey="Xue, Yuan" sort="Xue, Yuan" uniqKey="Xue Y" first="Yuan" last="Xue">Yuan Xue</name><affiliation><nlm:aff id="aff1">*Laboratory of Angiogenesis Research, Department of Microbiology, Tumor and Cell Biology, Karolinska Institute, 171 77 Stockholm, Sweden;</nlm:aff></affiliation></author><author><name sortKey="Cao, Renhai" sort="Cao, Renhai" uniqKey="Cao R" first="Renhai" last="Cao">Renhai Cao</name><affiliation><nlm:aff id="aff1">*Laboratory of Angiogenesis Research, Department of Microbiology, Tumor and Cell Biology, Karolinska Institute, 171 77 Stockholm, Sweden;</nlm:aff></affiliation></author><author><name sortKey="Nilsson, Daniel" sort="Nilsson, Daniel" uniqKey="Nilsson D" first="Daniel" last="Nilsson">Daniel Nilsson</name><affiliation><nlm:aff wicri:cut="; and" id="aff2">Department of Medical and Clinical Genetics, Institute of Biomedicine, the Sahlgrenska Academy, Göteborg University, Box 440, SE 405 30 Göteborg, Sweden</nlm:aff></affiliation></author><author><name sortKey="Chen, Shaohua" sort="Chen, Shaohua" uniqKey="Chen S" first="Shaohua" last="Chen">Shaohua Chen</name><affiliation><nlm:aff id="aff1">*Laboratory of Angiogenesis Research, Department of Microbiology, Tumor and Cell Biology, Karolinska Institute, 171 77 Stockholm, Sweden;</nlm:aff></affiliation></author><author><name sortKey="Westergren, Rickard" sort="Westergren, Rickard" uniqKey="Westergren R" first="Rickard" last="Westergren">Rickard Westergren</name><affiliation><nlm:aff wicri:cut="; and" id="aff2">Department of Medical and Clinical Genetics, Institute of Biomedicine, the Sahlgrenska Academy, Göteborg University, Box 440, SE 405 30 Göteborg, Sweden</nlm:aff></affiliation></author><author><name sortKey="Hedlund, Eva Maria" sort="Hedlund, Eva Maria" uniqKey="Hedlund E" first="Eva-Maria" last="Hedlund">Eva-Maria Hedlund</name><affiliation><nlm:aff id="aff1">*Laboratory of Angiogenesis Research, Department of Microbiology, Tumor and Cell Biology, Karolinska Institute, 171 77 Stockholm, Sweden;</nlm:aff></affiliation></author><author><name sortKey="Martijn, Cecile" sort="Martijn, Cecile" uniqKey="Martijn C" first="Cecile" last="Martijn">Cecile Martijn</name><affiliation><nlm:aff id="aff3">Biovitrum AB, Strandbergsgatan 49, P12-4, SE-112 76 Stockholm, Sweden</nlm:aff></affiliation></author><author><name sortKey="Rondahl, Lena" sort="Rondahl, Lena" uniqKey="Rondahl L" first="Lena" last="Rondahl">Lena Rondahl</name><affiliation><nlm:aff id="aff3">Biovitrum AB, Strandbergsgatan 49, P12-4, SE-112 76 Stockholm, Sweden</nlm:aff></affiliation></author><author><name sortKey="Krauli, Per" sort="Krauli, Per" uniqKey="Krauli P" first="Per" last="Krauli">Per Krauli</name><affiliation><nlm:aff id="aff3">Biovitrum AB, Strandbergsgatan 49, P12-4, SE-112 76 Stockholm, Sweden</nlm:aff></affiliation></author><author><name sortKey="Walum, Erik" sort="Walum, Erik" uniqKey="Walum E" first="Erik" last="Walum">Erik Walum</name><affiliation><nlm:aff id="aff3">Biovitrum AB, Strandbergsgatan 49, P12-4, SE-112 76 Stockholm, Sweden</nlm:aff></affiliation></author><author><name sortKey="Enerb Ck, Sven" sort="Enerb Ck, Sven" uniqKey="Enerb Ck S" first="Sven" last="Enerb Ck">Sven Enerb Ck</name><affiliation><nlm:aff wicri:cut="; and" id="aff2">Department of Medical and Clinical Genetics, Institute of Biomedicine, the Sahlgrenska Academy, Göteborg University, Box 440, SE 405 30 Göteborg, Sweden</nlm:aff></affiliation></author><author><name sortKey="Cao, Yihai" sort="Cao, Yihai" uniqKey="Cao Y" first="Yihai" last="Cao">Yihai Cao</name><affiliation><nlm:aff id="aff1">*Laboratory of Angiogenesis Research, Department of Microbiology, Tumor and Cell Biology, Karolinska Institute, 171 77 Stockholm, Sweden;</nlm:aff></affiliation></author></analytic><series><title level="j">Proceedings of the National Academy of Sciences of the United States of America</title><idno type="ISSN">0027-8424</idno><idno type="eISSN">1091-6490</idno><imprint><date when="2008">2008</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>Adipogenesis is spatiotemporally coupled to angiogenesis throughout adult life, and the interplay between these two processes is communicated by multiple factors. Here we show that in a transgenic mouse model, increased expression of forkhead box C2 (FOXC2) in the adipose tissue affects angiogenesis, vascular patterning, and functions. White and brown adipose tissues contain a considerably high density of microvessels appearing as vascular plexuses, which show redistribution of vascular smooth muscle cells and pericytes. Dysfunction of these primitive vessels is reflected by impairment of skin wound healing. We further provide a mechanistic insight of the vascular phenotype by showing that FOXC2 controls Ang-2 expression by direct activation of its promoter in adipocytes. Remarkably, an Ang-2-specific antagonist almost completely reverses this vascular phenotype. Thus, the FOXC2–Ang-2 signaling system is crucial for controlling adipose vascular function, which is part of an adaptation to increased adipose tissue metabolism.</p></div></front></TEI><pmc article-type="research-article"><pmc-comment>The publisher of this article does not allow downloading of the full text in XML form.</pmc-comment>
<front><journal-meta><journal-id journal-id-type="nlm-ta">Proc Natl Acad Sci U S A</journal-id><journal-id journal-id-type="hwp">pnas</journal-id><journal-id journal-id-type="pmc">pnas</journal-id><journal-id journal-id-type="publisher-id">PNAS</journal-id><journal-title-group><journal-title>Proceedings of the National Academy of Sciences of the United States of America</journal-title></journal-title-group><issn pub-type="ppub">0027-8424</issn><issn pub-type="epub">1091-6490</issn><publisher><publisher-name>National Academy of Sciences</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">18621714</article-id><article-id pub-id-type="pmc">2481379</article-id><article-id pub-id-type="publisher-id">3779</article-id><article-id pub-id-type="doi">10.1073/pnas.0802486105</article-id><article-categories><subj-group subj-group-type="heading"><subject>Biological Sciences</subject><subj-group><subject>Medical Sciences</subject></subj-group></subj-group></article-categories><title-group><article-title>FOXC2 controls Ang-2 expression and modulates angiogenesis, vascular patterning, remodeling, and functions in adipose tissue</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Xue</surname><given-names>Yuan</given-names></name><xref ref-type="aff" rid="aff1">*</xref></contrib><contrib contrib-type="author"><name><surname>Cao</surname><given-names>Renhai</given-names></name><xref ref-type="aff" rid="aff1">*</xref></contrib><contrib contrib-type="author"><name><surname>Nilsson</surname><given-names>Daniel</given-names></name><xref ref-type="aff" rid="aff2"><sup>†</sup></xref></contrib><contrib contrib-type="author"><name><surname>Chen</surname><given-names>Shaohua</given-names></name><xref ref-type="aff" rid="aff1">*</xref></contrib><contrib contrib-type="author"><name><surname>Westergren</surname><given-names>Rickard</given-names></name><xref ref-type="aff" rid="aff2"><sup>†</sup></xref></contrib><contrib contrib-type="author"><name><surname>Hedlund</surname><given-names>Eva-Maria</given-names></name><xref ref-type="aff" rid="aff1">*</xref></contrib><contrib contrib-type="author"><name><surname>Martijn</surname><given-names>Cecile</given-names></name><xref ref-type="aff" rid="aff3"><sup>‡</sup></xref></contrib><contrib contrib-type="author"><name><surname>Rondahl</surname><given-names>Lena</given-names></name><xref ref-type="aff" rid="aff3"><sup>‡</sup></xref></contrib><contrib contrib-type="author"><name><surname>Krauli</surname><given-names>Per</given-names></name><xref ref-type="aff" rid="aff3"><sup>‡</sup></xref></contrib><contrib contrib-type="author"><name><surname>Walum</surname><given-names>Erik</given-names></name><xref ref-type="aff" rid="aff3"><sup>‡</sup></xref></contrib><contrib contrib-type="author"><name><surname>Enerbäck</surname><given-names>Sven</given-names></name><xref ref-type="aff" rid="aff2"><sup>†</sup></xref></contrib><contrib contrib-type="author"><name><surname>Cao</surname><given-names>Yihai</given-names></name><xref ref-type="aff" rid="aff1">*</xref><xref ref-type="corresp" rid="cor1"><sup>§</sup></xref></contrib><aff id="aff1">*Laboratory of Angiogenesis Research, Department of Microbiology, Tumor and Cell Biology, Karolinska Institute, 171 77 Stockholm, Sweden;</aff><aff id="aff2"><sup>†</sup>Department of Medical and Clinical Genetics, Institute of Biomedicine, the Sahlgrenska Academy, Göteborg University, Box 440, SE 405 30 Göteborg, Sweden; and</aff><aff id="aff3"><sup>‡</sup>Biovitrum AB, Strandbergsgatan 49, P12-4, SE-112 76 Stockholm, Sweden</aff></contrib-group><author-notes><corresp id="cor1"><sup>§</sup>To whom correspondence should be addressed. E-mail: <email>yihai.cao@ki.se</email></corresp><fn fn-type="edited-by"><p>Edited by Tak Wah Mak, University of Toronto, Toronto, ON, Canada, and approved April 29, 2008</p></fn><fn fn-type="con"><p>Author contributions: Y.X., D.N., S.E., and Y.C. designed research; Y.X., R.C., D.N., S.C., R.W., C.M., L.R., and P.K. performed research; Y.X., R.C., D.N., R.W., E.-M.H., E.W., S.E., and Y.C. analyzed data; and Y.X., S.E., and Y.C. wrote the paper.</p></fn></author-notes><pub-date pub-type="ppub"><day>22</day><month>7</month><year>2008</year></pub-date><pub-date pub-type="epub"><day>11</day><month>7</month><year>2008</year></pub-date><volume>105</volume><issue>29</issue><fpage>10167</fpage><lpage>10172</lpage><history><date date-type="received"><day>17</day><month>3</month><year>2008</year></date></history><permissions><copyright-statement>© 2008 by The National Academy of Sciences of the USA</copyright-statement></permissions><self-uri xlink:title="pdf" xlink:type="simple" xlink:href="zpq02908010167.pdf"></self-uri><abstract><p>Adipogenesis is spatiotemporally coupled to angiogenesis throughout adult life, and the interplay between these two processes is communicated by multiple factors. Here we show that in a transgenic mouse model, increased expression of forkhead box C2 (FOXC2) in the adipose tissue affects angiogenesis, vascular patterning, and functions. White and brown adipose tissues contain a considerably high density of microvessels appearing as vascular plexuses, which show redistribution of vascular smooth muscle cells and pericytes. Dysfunction of these primitive vessels is reflected by impairment of skin wound healing. We further provide a mechanistic insight of the vascular phenotype by showing that FOXC2 controls Ang-2 expression by direct activation of its promoter in adipocytes. Remarkably, an Ang-2-specific antagonist almost completely reverses this vascular phenotype. Thus, the FOXC2–Ang-2 signaling system is crucial for controlling adipose vascular function, which is part of an adaptation to increased adipose tissue metabolism.</p></abstract><kwd-group><kwd>adipogenesis</kwd><kwd>neovascularization</kwd><kwd>wound healing</kwd><kwd>obesity</kwd><kwd>metabolism</kwd></kwd-group></article-meta></front></pmc></record>Pour manipuler ce document sous Unix (Dilib)
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