Angiopoietin-1, angiopoietin-2 and Tie-2 receptor expression in human dermal wound repair and scarring

Summary Background  The angiopoietin (Ang)/Tie‐2 ligand/receptor system is known to interact with the vascular endothelial growth factor (VEGF) pathway to determine the fate of blood vessels during angiogenesis. However, the precise contribution of this system to angiogenesis and the mechanisms of v...

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Veröffentlicht in:British journal of dermatology (1951) 2010-11, Vol.163 (5), p.920-927
Hauptverfasser: Staton, C.A., Valluru, M., Hoh, L., Reed, M.W.R., Brown, N.J.
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container_end_page 927
container_issue 5
container_start_page 920
container_title British journal of dermatology (1951)
container_volume 163
creator Staton, C.A.
Valluru, M.
Hoh, L.
Reed, M.W.R.
Brown, N.J.
description Summary Background  The angiopoietin (Ang)/Tie‐2 ligand/receptor system is known to interact with the vascular endothelial growth factor (VEGF) pathway to determine the fate of blood vessels during angiogenesis. However, the precise contribution of this system to angiogenesis and the mechanisms of vascular maturation and remodelling in human tissue repair have yet to be elucidated. Objectives  To examine the spatial and temporal expression of Ang‐1, Ang‐2, Tie‐2 and VEGF in relation to angiogenesis in human surgical wounds. Methods  Punch biopsies were taken either from normal unwounded skin (controls) during surgery or from mastectomy scars between 3 days and 2 years postsurgery. Ang‐1, Ang‐2, Tie‐2 and VEGF fibroblast/myofibroblast and endothelial expression were characterized by immunohistochemistry, analysed semiquantitatively and correlated with microvessel density (MVD) and scar age. Results  The expression of VEGF, Ang‐1, Ang‐2 and Tie‐2 in fibroblasts/myofibroblasts was increased significantly in early scars, decreased in older scars and was related to scar age (P 
doi_str_mv 10.1111/j.1365-2133.2010.09940.x
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However, the precise contribution of this system to angiogenesis and the mechanisms of vascular maturation and remodelling in human tissue repair have yet to be elucidated. Objectives  To examine the spatial and temporal expression of Ang‐1, Ang‐2, Tie‐2 and VEGF in relation to angiogenesis in human surgical wounds. Methods  Punch biopsies were taken either from normal unwounded skin (controls) during surgery or from mastectomy scars between 3 days and 2 years postsurgery. Ang‐1, Ang‐2, Tie‐2 and VEGF fibroblast/myofibroblast and endothelial expression were characterized by immunohistochemistry, analysed semiquantitatively and correlated with microvessel density (MVD) and scar age. Results  The expression of VEGF, Ang‐1, Ang‐2 and Tie‐2 in fibroblasts/myofibroblasts was increased significantly in early scars, decreased in older scars and was related to scar age (P &lt; 0·001) and MVD (P &lt; 0·0004), with strong correlations between all factors. In contrast, vascular expression of Ang‐1 was decreased slightly in early scars, vascular Ang‐2 remained constant and Tie‐2 vascular expression increased, although there were no correlations with scar age or MVD. Conclusions  These data demonstrate that angiopoietins and their receptor, Tie‐2, are expressed in both fibroblasts/myofibroblasts and endothelial cells in healing human wounds. Fibroblast/myofibroblast expression correlates with angiogenesis and VEGF expression, suggesting a role for the angiopoietin/Tie‐2 system in normal wound repair and scarring.</description><identifier>ISSN: 0007-0963</identifier><identifier>EISSN: 1365-2133</identifier><identifier>DOI: 10.1111/j.1365-2133.2010.09940.x</identifier><identifier>PMID: 20633009</identifier><identifier>CODEN: BJDEAZ</identifier><language>eng</language><publisher>Oxford, UK: Blackwell Publishing Ltd</publisher><subject>angiogenesis ; angiopoietin ; Angiopoietin-1 - metabolism ; Angiopoietin-2 - metabolism ; Biological and medical sciences ; Biopsy ; Cicatrix - metabolism ; Cicatrix - pathology ; Dermatology ; Endothelial Cells - metabolism ; Female ; Fibroblasts - metabolism ; Humans ; Immunohistochemistry ; Medical sciences ; Myofibroblasts - metabolism ; Neovascularization, Physiologic - physiology ; Receptor, TIE-2 - metabolism ; Skin - metabolism ; Skin - pathology ; Tie-2 ; Vascular Endothelial Growth Factor A - metabolism ; VEGF ; wound healing ; Wound Healing - physiology</subject><ispartof>British journal of dermatology (1951), 2010-11, Vol.163 (5), p.920-927</ispartof><rights>2010 The Authors. BJD © 2010 British Association of Dermatologists</rights><rights>2015 INIST-CNRS</rights><rights>2010 The Authors. 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However, the precise contribution of this system to angiogenesis and the mechanisms of vascular maturation and remodelling in human tissue repair have yet to be elucidated. Objectives  To examine the spatial and temporal expression of Ang‐1, Ang‐2, Tie‐2 and VEGF in relation to angiogenesis in human surgical wounds. Methods  Punch biopsies were taken either from normal unwounded skin (controls) during surgery or from mastectomy scars between 3 days and 2 years postsurgery. Ang‐1, Ang‐2, Tie‐2 and VEGF fibroblast/myofibroblast and endothelial expression were characterized by immunohistochemistry, analysed semiquantitatively and correlated with microvessel density (MVD) and scar age. Results  The expression of VEGF, Ang‐1, Ang‐2 and Tie‐2 in fibroblasts/myofibroblasts was increased significantly in early scars, decreased in older scars and was related to scar age (P &lt; 0·001) and MVD (P &lt; 0·0004), with strong correlations between all factors. In contrast, vascular expression of Ang‐1 was decreased slightly in early scars, vascular Ang‐2 remained constant and Tie‐2 vascular expression increased, although there were no correlations with scar age or MVD. Conclusions  These data demonstrate that angiopoietins and their receptor, Tie‐2, are expressed in both fibroblasts/myofibroblasts and endothelial cells in healing human wounds. Fibroblast/myofibroblast expression correlates with angiogenesis and VEGF expression, suggesting a role for the angiopoietin/Tie‐2 system in normal wound repair and scarring.</description><subject>angiogenesis</subject><subject>angiopoietin</subject><subject>Angiopoietin-1 - metabolism</subject><subject>Angiopoietin-2 - metabolism</subject><subject>Biological and medical sciences</subject><subject>Biopsy</subject><subject>Cicatrix - metabolism</subject><subject>Cicatrix - pathology</subject><subject>Dermatology</subject><subject>Endothelial Cells - metabolism</subject><subject>Female</subject><subject>Fibroblasts - metabolism</subject><subject>Humans</subject><subject>Immunohistochemistry</subject><subject>Medical sciences</subject><subject>Myofibroblasts - metabolism</subject><subject>Neovascularization, Physiologic - physiology</subject><subject>Receptor, TIE-2 - metabolism</subject><subject>Skin - metabolism</subject><subject>Skin - pathology</subject><subject>Tie-2</subject><subject>Vascular Endothelial Growth Factor A - metabolism</subject><subject>VEGF</subject><subject>wound healing</subject><subject>Wound Healing - physiology</subject><issn>0007-0963</issn><issn>1365-2133</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2010</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpNkU1v1DAQhi0EokvhL6BcEBeyjDOJHR84lEJb0FIuhUq9WE48KV7yhb1Rt_--TndZ8MUznue1ZD-MJRyWPK736yVHUaQZR1xmEE9BqRyW2ydscRg8ZQsAkCkogUfsRQhrAI5QwHN2lIFABFAL1pz0t24YB0cb16f8XWL-77PY2uTKUaw81TRuBp_QdvQUghv6xPXJr6kzfWLJd6ZN7oYp8p5G4_xjNNTGe9ffvmTPGtMGerXfj9mPs89Xpxfp6vv5l9OTVVpjKSElxUVVySzLKxSWC4tScgtFY0A2KqvyEmyJORcK86IylW2qsixJKGUbySHHY_Z2d-_ohz8ThY3uXKipbU1PwxS0FByQyzKL5Os9OVUdWT161xl_r_9-TQTe7AETX9E23vS1C_84RMlRFZH7sOPuXEv3hzkHPavSaz0b0bMRPavSj6r0Vn_8-mmuYj7d5V3Y0PaQN_63FhJloa8vz_XNxeXP1fXNNw34AKGWlPk</recordid><startdate>201011</startdate><enddate>201011</enddate><creator>Staton, C.A.</creator><creator>Valluru, M.</creator><creator>Hoh, L.</creator><creator>Reed, M.W.R.</creator><creator>Brown, N.J.</creator><general>Blackwell Publishing Ltd</general><general>Wiley-Blackwell</general><scope>BSCLL</scope><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>7X8</scope></search><sort><creationdate>201011</creationdate><title>Angiopoietin-1, angiopoietin-2 and Tie-2 receptor expression in human dermal wound repair and scarring</title><author>Staton, C.A. ; Valluru, M. ; Hoh, L. ; Reed, M.W.R. ; Brown, N.J.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3870-e916bb7224b36d16d3771d05fa07f92b480d834169345babdfb888e699df71043</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2010</creationdate><topic>angiogenesis</topic><topic>angiopoietin</topic><topic>Angiopoietin-1 - metabolism</topic><topic>Angiopoietin-2 - metabolism</topic><topic>Biological and medical sciences</topic><topic>Biopsy</topic><topic>Cicatrix - metabolism</topic><topic>Cicatrix - pathology</topic><topic>Dermatology</topic><topic>Endothelial Cells - metabolism</topic><topic>Female</topic><topic>Fibroblasts - metabolism</topic><topic>Humans</topic><topic>Immunohistochemistry</topic><topic>Medical sciences</topic><topic>Myofibroblasts - metabolism</topic><topic>Neovascularization, Physiologic - physiology</topic><topic>Receptor, TIE-2 - metabolism</topic><topic>Skin - metabolism</topic><topic>Skin - pathology</topic><topic>Tie-2</topic><topic>Vascular Endothelial Growth Factor A - metabolism</topic><topic>VEGF</topic><topic>wound healing</topic><topic>Wound Healing - physiology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Staton, C.A.</creatorcontrib><creatorcontrib>Valluru, M.</creatorcontrib><creatorcontrib>Hoh, L.</creatorcontrib><creatorcontrib>Reed, M.W.R.</creatorcontrib><creatorcontrib>Brown, N.J.</creatorcontrib><collection>Istex</collection><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>MEDLINE - Academic</collection><jtitle>British journal of dermatology (1951)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Staton, C.A.</au><au>Valluru, M.</au><au>Hoh, L.</au><au>Reed, M.W.R.</au><au>Brown, N.J.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Angiopoietin-1, angiopoietin-2 and Tie-2 receptor expression in human dermal wound repair and scarring</atitle><jtitle>British journal of dermatology (1951)</jtitle><addtitle>Br J Dermatol</addtitle><date>2010-11</date><risdate>2010</risdate><volume>163</volume><issue>5</issue><spage>920</spage><epage>927</epage><pages>920-927</pages><issn>0007-0963</issn><eissn>1365-2133</eissn><coden>BJDEAZ</coden><abstract>Summary Background  The angiopoietin (Ang)/Tie‐2 ligand/receptor system is known to interact with the vascular endothelial growth factor (VEGF) pathway to determine the fate of blood vessels during angiogenesis. However, the precise contribution of this system to angiogenesis and the mechanisms of vascular maturation and remodelling in human tissue repair have yet to be elucidated. Objectives  To examine the spatial and temporal expression of Ang‐1, Ang‐2, Tie‐2 and VEGF in relation to angiogenesis in human surgical wounds. Methods  Punch biopsies were taken either from normal unwounded skin (controls) during surgery or from mastectomy scars between 3 days and 2 years postsurgery. Ang‐1, Ang‐2, Tie‐2 and VEGF fibroblast/myofibroblast and endothelial expression were characterized by immunohistochemistry, analysed semiquantitatively and correlated with microvessel density (MVD) and scar age. Results  The expression of VEGF, Ang‐1, Ang‐2 and Tie‐2 in fibroblasts/myofibroblasts was increased significantly in early scars, decreased in older scars and was related to scar age (P &lt; 0·001) and MVD (P &lt; 0·0004), with strong correlations between all factors. In contrast, vascular expression of Ang‐1 was decreased slightly in early scars, vascular Ang‐2 remained constant and Tie‐2 vascular expression increased, although there were no correlations with scar age or MVD. Conclusions  These data demonstrate that angiopoietins and their receptor, Tie‐2, are expressed in both fibroblasts/myofibroblasts and endothelial cells in healing human wounds. Fibroblast/myofibroblast expression correlates with angiogenesis and VEGF expression, suggesting a role for the angiopoietin/Tie‐2 system in normal wound repair and scarring.</abstract><cop>Oxford, UK</cop><pub>Blackwell Publishing Ltd</pub><pmid>20633009</pmid><doi>10.1111/j.1365-2133.2010.09940.x</doi><tpages>8</tpages></addata></record>
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source Oxford University Press Journals All Titles (1996-Current); MEDLINE; Wiley Online Library Journals Frontfile Complete
subjects angiogenesis
angiopoietin
Angiopoietin-1 - metabolism
Angiopoietin-2 - metabolism
Biological and medical sciences
Biopsy
Cicatrix - metabolism
Cicatrix - pathology
Dermatology
Endothelial Cells - metabolism
Female
Fibroblasts - metabolism
Humans
Immunohistochemistry
Medical sciences
Myofibroblasts - metabolism
Neovascularization, Physiologic - physiology
Receptor, TIE-2 - metabolism
Skin - metabolism
Skin - pathology
Tie-2
Vascular Endothelial Growth Factor A - metabolism
VEGF
wound healing
Wound Healing - physiology
title Angiopoietin-1, angiopoietin-2 and Tie-2 receptor expression in human dermal wound repair and scarring
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