Upregulation of TGF-beta 1 expression may be necessary but is not sufficient for excessive scarring

Detalhes bibliográficos
Autor(a) principal: Campaner, Anelisa Bittencourt [UNIFESP]
Data de Publicação: 2006
Outros Autores: Ferreira, Lydia Masako [UNIFESP], Gragnani, Alfredo [UNIFESP], Bruder, Jan M., Cusick, Jennifer L., Morgan, Jeffrey R.
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Institucional da UNIFESP
Texto Completo: http://repositorio.unifesp.br/handle/11600/28854
http://dx.doi.org/10.1038/sj.jid.5700200
Resumo: Transforming growth factor beta 1 (TGF-beta 1) upregulation has been implicated in hypertrophic scars and keloids, but it is unclear if it is the cause or an effect of excessive scar formation. in this study, we overexpressed TGF-beta 1 in fibroblasts and characterized its role. Normal human dermal fibroblasts were genetically modified to overexpress TGF-beta 1 as the wild-type latent molecule or as a mutant constitutively active molecule. TGF-beta 1 secretion was measured, as were the effects of TGF-beta 1 upregulation on cell proliferation, expression of smooth muscle cell alpha actin (SMC alpha-actin) and ability to contract collagen lattices. Fibroblasts were implanted intradermally into athymic mice and tissue formation was analyzed over time by histology and immunostaining. Gene-modified fibroblasts secreted similar to 20 times the TGF-beta 1 released by control cells, but only cells expressing mutant TGF-beta 1 secreted it in the active form. Fibroblasts expressing the active TGF-beta 1 gene had increased levels of SMC alpha-actin and enhanced ability to contract a collagen lattice. After intradermal injection into athymic mice, only fibroblasts expressing active TGF-beta 1 formed keloid-like'' nodules containing collagen, which persisted longer than implants of the other cell types. We conclude that upregulation of TGF-beta 1 by fibroblasts may be necessary, but is not sufficient for excessive scarring. Needed are other signals to activate TGF-beta 1 and prolong cell persistence.
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spelling Campaner, Anelisa Bittencourt [UNIFESP]Ferreira, Lydia Masako [UNIFESP]Gragnani, Alfredo [UNIFESP]Bruder, Jan M.Cusick, Jennifer L.Morgan, Jeffrey R.Brown UnivUniversidade Federal de São Paulo (UNIFESP)Harvard UnivShriners Hosp Children2016-01-24T12:41:07Z2016-01-24T12:41:07Z2006-05-01Journal of Investigative Dermatology. New York: Nature Publishing Group, v. 126, n. 5, p. 1168-1176, 2006.0022-202Xhttp://repositorio.unifesp.br/handle/11600/28854http://dx.doi.org/10.1038/sj.jid.570020010.1038/sj.jid.5700200WOS:000238968700035Transforming growth factor beta 1 (TGF-beta 1) upregulation has been implicated in hypertrophic scars and keloids, but it is unclear if it is the cause or an effect of excessive scar formation. in this study, we overexpressed TGF-beta 1 in fibroblasts and characterized its role. Normal human dermal fibroblasts were genetically modified to overexpress TGF-beta 1 as the wild-type latent molecule or as a mutant constitutively active molecule. TGF-beta 1 secretion was measured, as were the effects of TGF-beta 1 upregulation on cell proliferation, expression of smooth muscle cell alpha actin (SMC alpha-actin) and ability to contract collagen lattices. Fibroblasts were implanted intradermally into athymic mice and tissue formation was analyzed over time by histology and immunostaining. Gene-modified fibroblasts secreted similar to 20 times the TGF-beta 1 released by control cells, but only cells expressing mutant TGF-beta 1 secreted it in the active form. Fibroblasts expressing the active TGF-beta 1 gene had increased levels of SMC alpha-actin and enhanced ability to contract a collagen lattice. After intradermal injection into athymic mice, only fibroblasts expressing active TGF-beta 1 formed keloid-like'' nodules containing collagen, which persisted longer than implants of the other cell types. We conclude that upregulation of TGF-beta 1 by fibroblasts may be necessary, but is not sufficient for excessive scarring. Needed are other signals to activate TGF-beta 1 and prolong cell persistence.Brown Univ, Dept Mol Pharmacol Physiol & Biotechnol, Providence, RI 02912 USAUniversidade Federal de São Paulo, Div Plast Surg, São Paulo, BrazilHarvard Univ, Sch Med, Ctr Engn Med & Surg, Massachusetts Gen Hosp, Boston, MA 02115 USAShriners Hosp Children, Boston, MA USAUniversidade Federal de São Paulo, Div Plast Surg, São Paulo, BrazilWeb of Science1168-1176engNature Publishing GroupJournal of Investigative DermatologyUpregulation of TGF-beta 1 expression may be necessary but is not sufficient for excessive scarringinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da UNIFESPinstname:Universidade Federal de São Paulo (UNIFESP)instacron:UNIFESP11600/288542022-07-08 10:22:11.875metadata only accessoai:repositorio.unifesp.br:11600/28854Repositório InstitucionalPUBhttp://www.repositorio.unifesp.br/oai/requestopendoar:34652022-07-08T13:22:11Repositório Institucional da UNIFESP - Universidade Federal de São Paulo (UNIFESP)false
dc.title.en.fl_str_mv Upregulation of TGF-beta 1 expression may be necessary but is not sufficient for excessive scarring
title Upregulation of TGF-beta 1 expression may be necessary but is not sufficient for excessive scarring
spellingShingle Upregulation of TGF-beta 1 expression may be necessary but is not sufficient for excessive scarring
Campaner, Anelisa Bittencourt [UNIFESP]
title_short Upregulation of TGF-beta 1 expression may be necessary but is not sufficient for excessive scarring
title_full Upregulation of TGF-beta 1 expression may be necessary but is not sufficient for excessive scarring
title_fullStr Upregulation of TGF-beta 1 expression may be necessary but is not sufficient for excessive scarring
title_full_unstemmed Upregulation of TGF-beta 1 expression may be necessary but is not sufficient for excessive scarring
title_sort Upregulation of TGF-beta 1 expression may be necessary but is not sufficient for excessive scarring
author Campaner, Anelisa Bittencourt [UNIFESP]
author_facet Campaner, Anelisa Bittencourt [UNIFESP]
Ferreira, Lydia Masako [UNIFESP]
Gragnani, Alfredo [UNIFESP]
Bruder, Jan M.
Cusick, Jennifer L.
Morgan, Jeffrey R.
author_role author
author2 Ferreira, Lydia Masako [UNIFESP]
Gragnani, Alfredo [UNIFESP]
Bruder, Jan M.
Cusick, Jennifer L.
Morgan, Jeffrey R.
author2_role author
author
author
author
author
dc.contributor.institution.none.fl_str_mv Brown Univ
Universidade Federal de São Paulo (UNIFESP)
Harvard Univ
Shriners Hosp Children
dc.contributor.author.fl_str_mv Campaner, Anelisa Bittencourt [UNIFESP]
Ferreira, Lydia Masako [UNIFESP]
Gragnani, Alfredo [UNIFESP]
Bruder, Jan M.
Cusick, Jennifer L.
Morgan, Jeffrey R.
description Transforming growth factor beta 1 (TGF-beta 1) upregulation has been implicated in hypertrophic scars and keloids, but it is unclear if it is the cause or an effect of excessive scar formation. in this study, we overexpressed TGF-beta 1 in fibroblasts and characterized its role. Normal human dermal fibroblasts were genetically modified to overexpress TGF-beta 1 as the wild-type latent molecule or as a mutant constitutively active molecule. TGF-beta 1 secretion was measured, as were the effects of TGF-beta 1 upregulation on cell proliferation, expression of smooth muscle cell alpha actin (SMC alpha-actin) and ability to contract collagen lattices. Fibroblasts were implanted intradermally into athymic mice and tissue formation was analyzed over time by histology and immunostaining. Gene-modified fibroblasts secreted similar to 20 times the TGF-beta 1 released by control cells, but only cells expressing mutant TGF-beta 1 secreted it in the active form. Fibroblasts expressing the active TGF-beta 1 gene had increased levels of SMC alpha-actin and enhanced ability to contract a collagen lattice. After intradermal injection into athymic mice, only fibroblasts expressing active TGF-beta 1 formed keloid-like'' nodules containing collagen, which persisted longer than implants of the other cell types. We conclude that upregulation of TGF-beta 1 by fibroblasts may be necessary, but is not sufficient for excessive scarring. Needed are other signals to activate TGF-beta 1 and prolong cell persistence.
publishDate 2006
dc.date.issued.fl_str_mv 2006-05-01
dc.date.accessioned.fl_str_mv 2016-01-24T12:41:07Z
dc.date.available.fl_str_mv 2016-01-24T12:41:07Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.citation.fl_str_mv Journal of Investigative Dermatology. New York: Nature Publishing Group, v. 126, n. 5, p. 1168-1176, 2006.
dc.identifier.uri.fl_str_mv http://repositorio.unifesp.br/handle/11600/28854
http://dx.doi.org/10.1038/sj.jid.5700200
dc.identifier.issn.none.fl_str_mv 0022-202X
dc.identifier.doi.none.fl_str_mv 10.1038/sj.jid.5700200
dc.identifier.wos.none.fl_str_mv WOS:000238968700035
identifier_str_mv Journal of Investigative Dermatology. New York: Nature Publishing Group, v. 126, n. 5, p. 1168-1176, 2006.
0022-202X
10.1038/sj.jid.5700200
WOS:000238968700035
url http://repositorio.unifesp.br/handle/11600/28854
http://dx.doi.org/10.1038/sj.jid.5700200
dc.language.iso.fl_str_mv eng
language eng
dc.relation.ispartof.none.fl_str_mv Journal of Investigative Dermatology
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv 1168-1176
dc.publisher.none.fl_str_mv Nature Publishing Group
publisher.none.fl_str_mv Nature Publishing Group
dc.source.none.fl_str_mv reponame:Repositório Institucional da UNIFESP
instname:Universidade Federal de São Paulo (UNIFESP)
instacron:UNIFESP
instname_str Universidade Federal de São Paulo (UNIFESP)
instacron_str UNIFESP
institution UNIFESP
reponame_str Repositório Institucional da UNIFESP
collection Repositório Institucional da UNIFESP
repository.name.fl_str_mv Repositório Institucional da UNIFESP - Universidade Federal de São Paulo (UNIFESP)
repository.mail.fl_str_mv
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