Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 1 de 1
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
J Invest Dermatol ; 139(7): 1497-1505.e5, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-30684555

RESUMO

Mutations in the gene encoding collagen VII cause the devastating blistering disease recessive dystrophic epidermolysis bullosa (RDEB). RDEB is characterized by severe skin fragility and nonhealing wounds aggravated by scarring and fibrosis. We previously showed that TSP1 is increased in RDEB fibroblasts. Because transforming growth factor-ß (TGF-ß) signaling is also increased in RDEB, and TSP1 is known to activate TGF-ß, we investigated the role of TSP1 in TGF-ß signaling in RDEB patient cells. Knockdown of TSP1 reduced phosphorylation of smad3 (a downstream target of TGF-ß signaling) in RDEB primary fibroblasts, whereas overexpression of collagen VII reduced phosphorylation of smad3. Furthermore, inhibition of TSP1 binding to the LAP/TGF-ß complex decreased fibrosis in engineered extracellular matrix formed by RDEB fibroblasts, as evaluated by picrosirius red staining and analyses of birefringent collagen fibrillar deposits. We show that collagen VII binds TSP1, which could potentially limit TSP1-LAP association and subsequent TGF-ß activation. Our study suggests a previously unreported mechanism for increased TGF-ß signaling in the absence of collagen VII in RDEB patient skin. Moreover, these data identify TSP1 as a possible target for reducing fibrosis in the tumor-promoting dermal microenvironment of RDEB patients.


Assuntos
Epidermólise Bolhosa Distrófica/metabolismo , Matriz Extracelular/metabolismo , Fibroblastos/metabolismo , Pele/patologia , Trombospondina 1/metabolismo , Fator de Crescimento Transformador beta/metabolismo , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Células Cultivadas , Criança , Pré-Escolar , Colágeno Tipo VII/genética , Epidermólise Bolhosa Distrófica/genética , Feminino , Fibroblastos/patologia , Fibrose , Técnicas de Silenciamento de Genes , Genes Recessivos , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Mutação/genética , Fosforilação , Ligação Proteica , Transdução de Sinais , Proteína Smad3/metabolismo , Trombospondina 1/genética , Microambiente Tumoral , Adulto Jovem
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...