Loss of serum response factor in keratinocytes results in hyperproliferative skin disease in mice.

Détails

ID Serval
serval:BIB_A96F3D1C612B
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Loss of serum response factor in keratinocytes results in hyperproliferative skin disease in mice.
Périodique
Journal of Clinical Investigation
Auteur(s)
Koegel H., von Tobel L., Schäfer M., Alberti S., Kremmer E., Mauch C., Hohl D., Wang X.J., Beer H.D., Bloch W., Nordheim A., Werner S.
ISSN
1558-8238[electronic]
Statut éditorial
Publié
Date de publication
2009
Volume
119
Numéro
4
Pages
899-910
Langue
anglais
Résumé
The transcription factor serum response factor (SRF) plays a crucial role in the development of several organs. However, its role in the skin has not been explored. Here, we show that keratinocytes in normal human and mouse skin expressed high levels of SRF but that SRF expression was strongly downregulated in the hyperproliferative epidermis of wounded and psoriatic skin. Keratinocyte-specific deletion within the mouse SRF locus during embryonic development caused edema and skin blistering, and all animals died in utero. Postnatal loss of mouse SRF in keratinocytes resulted in the development of psoriasis-like skin lesions. These lesions were characterized by inflammation, hyperproliferation, and abnormal differentiation of keratinocytes as well as by disruption of the actin cytoskeleton. Ultrastructural analysis revealed markedly reduced cell-cell and cell-matrix contacts and loss of cell compaction in all epidermal layers. siRNA-mediated knockdown of SRF in primary human keratinocytes revealed that the cytoskeletal abnormalities and adhesion defects were a direct consequence of the loss of SRF. In contrast, the hyperproliferation observed in vivo was an indirect effect that was most likely a consequence of the inflammation. These results reveal that loss of SRF disrupts epidermal homeostasis and strongly suggest its involvement in the pathogenesis of hyperproliferative skin diseases, including psoriasis.
Mots-clé
Actins/metabolism, Animals, Base Sequence, Cell Adhesion, Cell Differentiation, Cell Movement, Cell Proliferation, Cells, Cultured, DNA Primers/genetics, Desmosomes/pathology, Down-Regulation, Female, Humans, Keratinocytes/metabolism, Keratinocytes/pathology, Mice, Mice, Mutant Strains, Mice, Transgenic, Pregnancy, Psoriasis/genetics, Psoriasis/metabolism, RNA, Small Interfering/genetics, Serum Response Factor/antagonists & inhibitors, Serum Response Factor/deficiency, Skin/injuries, Skin/metabolism, Skin Diseases/genetics, Skin Diseases/metabolism, Wound Healing/genetics, Wound Healing/physiology
Pubmed
Web of science
Open Access
Oui
Création de la notice
09/02/2010 14:01
Dernière modification de la notice
20/08/2019 16:13
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