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

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

Autor Campaner, Anelisa Bittencourt Autor UNIFESP Google Scholar
Ferreira, Lydia Masako Autor UNIFESP Google Scholar
Gragnani, Alfredo Autor UNIFESP Google Scholar
Bruder, Jan M. Google Scholar
Cusick, Jennifer L. Google Scholar
Morgan, Jeffrey R. Google Scholar
Instituição Brown Univ
Universidade Federal de São Paulo (UNIFESP)
Harvard Univ
Shriners Hosp Children
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.
Idioma Inglês
Data de publicação 2006-05-01
Publicado em Journal of Investigative Dermatology. New York: Nature Publishing Group, v. 126, n. 5, p. 1168-1176, 2006.
ISSN 0022-202X (Sherpa/Romeo, fator de impacto)
Publicador Nature Publishing Group
Extensão 1168-1176
Fonte http://dx.doi.org/10.1038/sj.jid.5700200
Direito de acesso Acesso aberto Open Access
Tipo Artigo
Web of Science WOS:000238968700035
Endereço permanente http://repositorio.unifesp.br/handle/11600/28854

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