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 Cell Sci ; 118(Pt 15): 3387-95, 2005 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-16079282

RESUMO

Mice deficient for cathepsin L (CTSL) show epidermal hyperplasia due to a hyperproliferation of basal keratinocytes. Here we show that the critical function of CTSL in the skin is keratinocyte specific. This is revealed by transgenic re-expression of CTSL in the keratinocytes of ctsl-/- mice, resulting in a rescue of the ctsl-/- skin phenotype. Cultivation of primary mouse keratinocytes with fibroblast- and keratinocyte-conditioned media, as well as heterologous organotypic co-cultures of mouse fibroblasts and human keratinocytes, showed that the altered keratinocyte proliferation is caused primarily by CTSL-deficiency in keratinocytes. In the absence of EGF, wild type and CTSL-knockout keratinocytes proliferate with the same rates, while in presence of EGF, ctsl-/- keratinocytes showed enhanced proliferation compared with controls. Internalization and degradation of radioactively labeled EGF was identical in both ctsl-/- and ctsl+/+ keratinocytes. However, ctsl-/- keratinocytes recycled more EGF to the cell surface, where it is bound to the EGF-receptor, which is also more abundant in ctsl-/- cells. We conclude that the hyperproliferation of keratinocytes in CTSL-knockout mice is caused by an enhanced recycling of growth factors and growth factor receptors from the endosomes to the keratinocyte plasma membrane, which result in sustained growth stimulation.


Assuntos
Catepsinas/metabolismo , Proliferação de Células/efeitos dos fármacos , Cisteína Endopeptidases/metabolismo , Fator de Crescimento Epidérmico/metabolismo , Queratinócitos/metabolismo , Lisossomos/enzimologia , Animais , Comunicação Autócrina/fisiologia , Catepsina L , Catepsinas/deficiência , Catepsinas/genética , Cisteína Endopeptidases/química , Cisteína Endopeptidases/deficiência , Cisteína Endopeptidases/genética , Fator de Crescimento Epidérmico/farmacologia , Receptores ErbB/metabolismo , Genótipo , Humanos , Queratina-14 , Queratinócitos/citologia , Queratinócitos/efeitos dos fármacos , Queratinas/genética , Queratinas/metabolismo , Camundongos , Camundongos Knockout , Camundongos Transgênicos , Fenótipo , Regiões Promotoras Genéticas , Pele/citologia , Fatores de Tempo
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA