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Decreased expression of inhibitory SMAD6 and SMAD7 in keloid scarring
Keloids are benign skin tumours occurring during wound healing in genetically predisposed patients. They are characterised by an abnormal deposition of extracellular matrix components, in particular collagen. There is evidence that transforming growth factor-beta (TGFβ) is involved in keloid formati...
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Published in: | Journal of plastic, reconstructive & aesthetic surgery reconstructive & aesthetic surgery, 2006-01, Vol.59 (3), p.221-229 |
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description | Keloids are benign skin tumours occurring during wound healing in genetically predisposed patients. They are characterised by an abnormal deposition of extracellular matrix components, in particular collagen. There is evidence that transforming growth factor-beta (TGFβ) is involved in keloid formation. SMAD proteins play a crucial role in TGFβ signaling and in terminating the TGFβ signal by a negative feedback loop through SMAD6 and 7. It is unclear how TGFβ signalling is connected to the pathogenesis of keloids. Therefore, we investigated the expression of SMAD mRNA and proteins in keloids, in normal skin and in normal scars.
Dermal fibroblasts were obtained from punch-biopsies of keloids, normal scars and normal skin. Cells were stimulated with TGFβ1 and the expression of SMAD2, 3, 4, 6 and 7 mRNA was analysed by real time RT-PCR. Protein expression was determined by Western blot analysis.
Our data demonstrate a decreased mRNA expression of the inhibitory SMAD6 and 7 in keloid fibroblasts as compared to normal scar (
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doi_str_mv | 10.1016/j.bjps.2005.06.010 |
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fullrecord | <record><control><sourceid>proquest_swepu</sourceid><recordid>TN_cdi_swepub_primary_oai_DiVA_org_liu_12814</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><els_id>S0007122605002705</els_id><sourcerecordid>67931485</sourcerecordid><originalsourceid>FETCH-LOGICAL-c487t-40bf885adb1268c0497bff61b401bd9abf140cfbfb7a39786f8bf1b3f22da48b3</originalsourceid><addsrcrecordid>eNp9kE1P3DAQhq2qqHz1D_RQ5VJOJNiJYztSL6tdviRQD7RcLX-MqbfZONibUv59vewKbpxmNPPMq9GD0BeCK4IJO1tWejmmqsa4rTCrMMEf0AERXJS4bbqPuedUlEyQdh8dprTEmDaEtp_QPmGMM1qLA3S-ABNBJbAF_BsjpOTDUARX-OG3134d4nNxdztbsEIN9qXjeVX8gT54WySjYvTDwzHac6pP8HlXj9Cvi_Of86vy5sfl9Xx2Uxoq-LqkWDshWmU1qZkwmHZcO8eIppho2yntCMXGaae5ajoumBN5pBtX11ZRoZsjdLrNTU8wTlqO0a9UfJZBebnw9zMZ4oPs_SRJLQjN-MkWH2N4nCCt5conA32vBghTkox3WYhoM1hvQRNDShHcazLBcuNaLuXGtdy4lpjJ7Doffd2lT3oF9u1kJzcD33aAyqJ6F9VgfHrjeMsy1WXu-5aDrO6vhyiT8TAYsD6CWUsb_Ht__AeLDZyN</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>67931485</pqid></control><display><type>article</type><title>Decreased expression of inhibitory SMAD6 and SMAD7 in keloid scarring</title><source>ScienceDirect Journals</source><creator>Yu, Haiyan ; Bock, Oliver ; Bayat, Ardeshir ; Ferguson, Mark W.J. ; Mrowietz, Ulrich</creator><creatorcontrib>Yu, Haiyan ; Bock, Oliver ; Bayat, Ardeshir ; Ferguson, Mark W.J. ; Mrowietz, Ulrich</creatorcontrib><description>Keloids are benign skin tumours occurring during wound healing in genetically predisposed patients. They are characterised by an abnormal deposition of extracellular matrix components, in particular collagen. There is evidence that transforming growth factor-beta (TGFβ) is involved in keloid formation. SMAD proteins play a crucial role in TGFβ signaling and in terminating the TGFβ signal by a negative feedback loop through SMAD6 and 7. It is unclear how TGFβ signalling is connected to the pathogenesis of keloids. Therefore, we investigated the expression of SMAD mRNA and proteins in keloids, in normal skin and in normal scars.
Dermal fibroblasts were obtained from punch-biopsies of keloids, normal scars and normal skin. Cells were stimulated with TGFβ1 and the expression of SMAD2, 3, 4, 6 and 7 mRNA was analysed by real time RT-PCR. Protein expression was determined by Western blot analysis.
Our data demonstrate a decreased mRNA expression of the inhibitory SMAD6 and 7 in keloid fibroblasts as compared to normal scar (
p<0.01) and normal skin fibroblasts (
p<0.05). SMAD3 mRNA was found to be lower in keloids (
p<0.01) and in normal scar fibroblasts (
p<0.001) compared to normal skin fibroblasts.
Our data showed for the first time a decreased expression of the inhibitory SMAD6 and SMAD7 in keloid fibroblasts. This could explain why TGFβ signaling is not terminated in keloids leading to overexpression of extracellularmatrix in keloids. These data support a possible role of SMAD6 and 7 in the pathogenesis of keloids.</description><identifier>ISSN: 1748-6815</identifier><identifier>EISSN: 1878-0539</identifier><identifier>DOI: 10.1016/j.bjps.2005.06.010</identifier><identifier>PMID: 16676428</identifier><language>eng</language><publisher>Oxford: Elsevier Ltd</publisher><subject>Biological and medical sciences ; Blotting, Western ; Cells, Cultured ; Dermatology ; Fibroblasts - metabolism ; Humans ; Keloid - metabolism ; Keloids ; Medical sciences ; MEDICIN ; MEDICINE ; Reverse Transcriptase Polymerase Chain Reaction ; RNA, Messenger - metabolism ; Skin involvement in other diseases. Miscellaneous. General aspects ; SMAD ; Smad6 Protein - metabolism ; Smad7 Protein - metabolism ; Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases ; TGFβ ; TGFβ signalling ; Transforming Growth Factor beta - pharmacology ; Transforming Growth Factor beta1</subject><ispartof>Journal of plastic, reconstructive & aesthetic surgery, 2006-01, Vol.59 (3), p.221-229</ispartof><rights>2005 The British Association of Plastic Surgeons</rights><rights>2006 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c487t-40bf885adb1268c0497bff61b401bd9abf140cfbfb7a39786f8bf1b3f22da48b3</citedby><cites>FETCH-LOGICAL-c487t-40bf885adb1268c0497bff61b401bd9abf140cfbfb7a39786f8bf1b3f22da48b3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,780,784,885,27924,27925</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=17562839$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/16676428$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-12814$$DView record from Swedish Publication Index$$Hfree_for_read</backlink></links><search><creatorcontrib>Yu, Haiyan</creatorcontrib><creatorcontrib>Bock, Oliver</creatorcontrib><creatorcontrib>Bayat, Ardeshir</creatorcontrib><creatorcontrib>Ferguson, Mark W.J.</creatorcontrib><creatorcontrib>Mrowietz, Ulrich</creatorcontrib><title>Decreased expression of inhibitory SMAD6 and SMAD7 in keloid scarring</title><title>Journal of plastic, reconstructive & aesthetic surgery</title><addtitle>J Plast Reconstr Aesthet Surg</addtitle><description>Keloids are benign skin tumours occurring during wound healing in genetically predisposed patients. They are characterised by an abnormal deposition of extracellular matrix components, in particular collagen. There is evidence that transforming growth factor-beta (TGFβ) is involved in keloid formation. SMAD proteins play a crucial role in TGFβ signaling and in terminating the TGFβ signal by a negative feedback loop through SMAD6 and 7. It is unclear how TGFβ signalling is connected to the pathogenesis of keloids. Therefore, we investigated the expression of SMAD mRNA and proteins in keloids, in normal skin and in normal scars.
Dermal fibroblasts were obtained from punch-biopsies of keloids, normal scars and normal skin. Cells were stimulated with TGFβ1 and the expression of SMAD2, 3, 4, 6 and 7 mRNA was analysed by real time RT-PCR. Protein expression was determined by Western blot analysis.
Our data demonstrate a decreased mRNA expression of the inhibitory SMAD6 and 7 in keloid fibroblasts as compared to normal scar (
p<0.01) and normal skin fibroblasts (
p<0.05). SMAD3 mRNA was found to be lower in keloids (
p<0.01) and in normal scar fibroblasts (
p<0.001) compared to normal skin fibroblasts.
Our data showed for the first time a decreased expression of the inhibitory SMAD6 and SMAD7 in keloid fibroblasts. This could explain why TGFβ signaling is not terminated in keloids leading to overexpression of extracellularmatrix in keloids. These data support a possible role of SMAD6 and 7 in the pathogenesis of keloids.</description><subject>Biological and medical sciences</subject><subject>Blotting, Western</subject><subject>Cells, Cultured</subject><subject>Dermatology</subject><subject>Fibroblasts - metabolism</subject><subject>Humans</subject><subject>Keloid - metabolism</subject><subject>Keloids</subject><subject>Medical sciences</subject><subject>MEDICIN</subject><subject>MEDICINE</subject><subject>Reverse Transcriptase Polymerase Chain Reaction</subject><subject>RNA, Messenger - metabolism</subject><subject>Skin involvement in other diseases. Miscellaneous. General aspects</subject><subject>SMAD</subject><subject>Smad6 Protein - metabolism</subject><subject>Smad7 Protein - metabolism</subject><subject>Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases</subject><subject>TGFβ</subject><subject>TGFβ signalling</subject><subject>Transforming Growth Factor beta - pharmacology</subject><subject>Transforming Growth Factor beta1</subject><issn>1748-6815</issn><issn>1878-0539</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2006</creationdate><recordtype>article</recordtype><recordid>eNp9kE1P3DAQhq2qqHz1D_RQ5VJOJNiJYztSL6tdviRQD7RcLX-MqbfZONibUv59vewKbpxmNPPMq9GD0BeCK4IJO1tWejmmqsa4rTCrMMEf0AERXJS4bbqPuedUlEyQdh8dprTEmDaEtp_QPmGMM1qLA3S-ABNBJbAF_BsjpOTDUARX-OG3134d4nNxdztbsEIN9qXjeVX8gT54WySjYvTDwzHac6pP8HlXj9Cvi_Of86vy5sfl9Xx2Uxoq-LqkWDshWmU1qZkwmHZcO8eIppho2yntCMXGaae5ajoumBN5pBtX11ZRoZsjdLrNTU8wTlqO0a9UfJZBebnw9zMZ4oPs_SRJLQjN-MkWH2N4nCCt5conA32vBghTkox3WYhoM1hvQRNDShHcazLBcuNaLuXGtdy4lpjJ7Doffd2lT3oF9u1kJzcD33aAyqJ6F9VgfHrjeMsy1WXu-5aDrO6vhyiT8TAYsD6CWUsb_Ht__AeLDZyN</recordid><startdate>20060101</startdate><enddate>20060101</enddate><creator>Yu, Haiyan</creator><creator>Bock, Oliver</creator><creator>Bayat, Ardeshir</creator><creator>Ferguson, Mark W.J.</creator><creator>Mrowietz, Ulrich</creator><general>Elsevier Ltd</general><general>Elsevier</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>ADTPV</scope><scope>AOWAS</scope><scope>DG8</scope></search><sort><creationdate>20060101</creationdate><title>Decreased expression of inhibitory SMAD6 and SMAD7 in keloid scarring</title><author>Yu, Haiyan ; Bock, Oliver ; Bayat, Ardeshir ; Ferguson, Mark W.J. ; Mrowietz, Ulrich</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c487t-40bf885adb1268c0497bff61b401bd9abf140cfbfb7a39786f8bf1b3f22da48b3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2006</creationdate><topic>Biological and medical sciences</topic><topic>Blotting, Western</topic><topic>Cells, Cultured</topic><topic>Dermatology</topic><topic>Fibroblasts - metabolism</topic><topic>Humans</topic><topic>Keloid - metabolism</topic><topic>Keloids</topic><topic>Medical sciences</topic><topic>MEDICIN</topic><topic>MEDICINE</topic><topic>Reverse Transcriptase Polymerase Chain Reaction</topic><topic>RNA, Messenger - metabolism</topic><topic>Skin involvement in other diseases. Miscellaneous. General aspects</topic><topic>SMAD</topic><topic>Smad6 Protein - metabolism</topic><topic>Smad7 Protein - metabolism</topic><topic>Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases</topic><topic>TGFβ</topic><topic>TGFβ signalling</topic><topic>Transforming Growth Factor beta - pharmacology</topic><topic>Transforming Growth Factor beta1</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Yu, Haiyan</creatorcontrib><creatorcontrib>Bock, Oliver</creatorcontrib><creatorcontrib>Bayat, Ardeshir</creatorcontrib><creatorcontrib>Ferguson, Mark W.J.</creatorcontrib><creatorcontrib>Mrowietz, Ulrich</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>SwePub</collection><collection>SwePub Articles</collection><collection>SWEPUB Linköpings universitet</collection><jtitle>Journal of plastic, reconstructive & aesthetic surgery</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Yu, Haiyan</au><au>Bock, Oliver</au><au>Bayat, Ardeshir</au><au>Ferguson, Mark W.J.</au><au>Mrowietz, Ulrich</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Decreased expression of inhibitory SMAD6 and SMAD7 in keloid scarring</atitle><jtitle>Journal of plastic, reconstructive & aesthetic surgery</jtitle><addtitle>J Plast Reconstr Aesthet Surg</addtitle><date>2006-01-01</date><risdate>2006</risdate><volume>59</volume><issue>3</issue><spage>221</spage><epage>229</epage><pages>221-229</pages><issn>1748-6815</issn><eissn>1878-0539</eissn><abstract>Keloids are benign skin tumours occurring during wound healing in genetically predisposed patients. They are characterised by an abnormal deposition of extracellular matrix components, in particular collagen. There is evidence that transforming growth factor-beta (TGFβ) is involved in keloid formation. SMAD proteins play a crucial role in TGFβ signaling and in terminating the TGFβ signal by a negative feedback loop through SMAD6 and 7. It is unclear how TGFβ signalling is connected to the pathogenesis of keloids. Therefore, we investigated the expression of SMAD mRNA and proteins in keloids, in normal skin and in normal scars.
Dermal fibroblasts were obtained from punch-biopsies of keloids, normal scars and normal skin. Cells were stimulated with TGFβ1 and the expression of SMAD2, 3, 4, 6 and 7 mRNA was analysed by real time RT-PCR. Protein expression was determined by Western blot analysis.
Our data demonstrate a decreased mRNA expression of the inhibitory SMAD6 and 7 in keloid fibroblasts as compared to normal scar (
p<0.01) and normal skin fibroblasts (
p<0.05). SMAD3 mRNA was found to be lower in keloids (
p<0.01) and in normal scar fibroblasts (
p<0.001) compared to normal skin fibroblasts.
Our data showed for the first time a decreased expression of the inhibitory SMAD6 and SMAD7 in keloid fibroblasts. This could explain why TGFβ signaling is not terminated in keloids leading to overexpression of extracellularmatrix in keloids. These data support a possible role of SMAD6 and 7 in the pathogenesis of keloids.</abstract><cop>Oxford</cop><pub>Elsevier Ltd</pub><pmid>16676428</pmid><doi>10.1016/j.bjps.2005.06.010</doi><tpages>9</tpages></addata></record> |
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subjects | Biological and medical sciences Blotting, Western Cells, Cultured Dermatology Fibroblasts - metabolism Humans Keloid - metabolism Keloids Medical sciences MEDICIN MEDICINE Reverse Transcriptase Polymerase Chain Reaction RNA, Messenger - metabolism Skin involvement in other diseases. Miscellaneous. General aspects SMAD Smad6 Protein - metabolism Smad7 Protein - metabolism Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases TGFβ TGFβ signalling Transforming Growth Factor beta - pharmacology Transforming Growth Factor beta1 |
title | Decreased expression of inhibitory SMAD6 and SMAD7 in keloid scarring |
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