Titre
Loss of serum response factor in keratinocytes results in hyperproliferative skin disease in mice.
Type
article
Institution
UNIL/CHUV/Unisanté + institutions partenaires
Périodique
Auteur(s)
Koegel, H.
Auteure/Auteur
von Tobel, L.
Auteure/Auteur
Schäfer, M.
Auteure/Auteur
Alberti, S.
Auteure/Auteur
Kremmer, E.
Auteure/Auteur
Mauch, C.
Auteure/Auteur
Hohl, D.
Auteure/Auteur
Wang, X.J.
Auteure/Auteur
Beer, H.D.
Auteure/Auteur
Bloch, W.
Auteure/Auteur
Nordheim, A.
Auteure/Auteur
Werner, S.
Auteure/Auteur
Liens vers les personnes
Liens vers les unités
ISSN
1558-8238[electronic]
Statut éditorial
Publié
Date de publication
2009
Volume
119
Numéro
4
Première page
899
Dernière page/numéro d’article
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.
Sujets
PID Serval
serval:BIB_A96F3D1C612B
PMID
Open Access
Oui
Date de création
2010-02-09T12:01:59.623Z
Date de création dans IRIS
2025-05-21T02:57:32Z