Epidermal ADAM17 maintains the skin barrier by regulating EGFR ligand-dependent terminal keratinocyte differentiation

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Epidermal ADAM17 maintains the skin barrier by regulating EGFR ligand-dependent terminal keratinocyte differentiation

ADAM17 (a disintegrin and metalloproteinase 17) is ubiquitously expressed and cleaves membrane proteins, such as epidermal growth factor receptor (EGFR) ligands, l-selectin, and TNF, from the cell surface, thus regulating responses to tissue injury and inflammation. However, little is currently known about its role in skin homeostasis. We show that mice lacking ADAM17 in keratinocytes (A17(ΔKC)...

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ADAM17/EGFR axis promotes transglutaminase-dependent skin barrier formation through phosholipase C γ1 and protein kinase C pathways

The vitally important skin barrier is formed by extensive cross-linking activity of transglutaminases (TGs) during terminal epidermal differentiation. We have previously shown that epidermal deficiency of a disintegrin and metalloproteinase 17 (ADAM17), the principal EGFR ligand sheddase, results in postnatal skin barrier defects in mice due to impeded TG activity. However, the mechanism by whi...

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Histamine suppresses epidermal keratinocyte differentiation and impairs skin barrier function in a human skin model

BACKGROUND Defects in keratinocyte differentiation and skin barrier are important features of inflammatory skin diseases like atopic dermatitis. Mast cells and their main mediator histamine are abundant in inflamed skin and thus may contribute to disease pathogenesis. METHODS Human primary keratinocytes were cultured under differentiation-promoting conditions in the presence and absence of hi...

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EGFR regulation of epidermal barrier function.

Keratinocyte terminal differentiation is the process that ultimately forms the epidermal barrier that is essential for mammalian survival. This process is controlled, in part, by signal transduction and gene expression mechanisms, and the epidermal growth factor receptor (EGFR) is known to be an important regulator of multiple epidermal functions. Using microarray analysis of a confluent cell d...

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Psoriasis is characterized by altered epidermal expression of caspase 14, a novel regulator of keratinocyte terminal differentiation and barrier formation.

Caspases are a family of cysteine proteases involved in the effector arm of physiologic cell death [1]. In 1998, a novel caspase designated ‘‘caspase 14’’ was described in embryonic and adult tissues, especially epidermal keratinocytes [2—4]. Unlike other caspases (such as 3, 6 and 7), caspase 14 is not processed by typical death stimuli or activated during apoptosis induced by ultraviolet irra...

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ژورنال

عنوان ژورنال: Journal of Experimental Medicine

سال: 2012

ISSN: 1540-9538,0022-1007

DOI: 10.1084/jem.2011225820913c