title: The epidermal barrier function is dependent on the serine protease CAP1/Prss8.
abstract: Serine proteases are proteolytic enzymes that are involved in the regulation of various physiological processes. We generated mice lacking the membrane-anchored channel-activating serine protease (CAP) 1 (also termed protease serine S1 family member 8 [Prss8] and prostasin) in skin, and these mice died within 60 h after birth. They presented a lower body weight and exhibited severe malformation of the stratum corneum (SC). This aberrant skin development was accompanied by an impaired skin barrier function, as evidenced by dehydration and skin permeability assay and transepidermal water loss measurements leading to rapid, fatal dehydration. Analysis of differentiation markers revealed no major alterations in CAP1/Prss8-deficient skin even though the epidermal deficiency of CAP1/Prss8 expression disturbs SC lipid composition, corneocyte morphogenesis, and the processing of profilaggrin. The examination of tight junction proteins revealed an absence of occludin, which did not prevent the diffusion of subcutaneously injected tracer (approximately 600 D) toward the skin surface. This study shows that CAP1/Prss8 expression in the epidermis is crucial for the epidermal permeability barrier and is, thereby, indispensable for postnatal survival.
authors.affiliation: Département de Pharmacologie et de Toxicologie, Université de Lausanne, CH-1005 Lausanne, Switzerland.
authors.forename: Céline
authors.initials: C
authors.lastname: Leyvraz
authors.forename: Roch-Philippe
authors.initials: RP
authors.lastname: Charles
authors.forename: Isabelle
authors.initials: I
authors.lastname: Rubera
authors.forename: Marjorie
authors.initials: M
authors.lastname: Guitard
authors.forename: Samuel
authors.initials: S
authors.lastname: Rotman
authors.forename: Bernadette
authors.initials: B
authors.lastname: Breiden
authors.forename: Konrad
authors.initials: K
authors.lastname: Sandhoff
authors.forename: Edith
authors.initials: E
authors.lastname: Hummler
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000502:physiology*; D003681:Dehydration / Q000235:genetics / Q000401:mortality; D004817:Epidermis / Q000201:enzymology / Q000473:pathology / Q000502:physiology*; D000091344:Filaggrin Proteins; D007381:Intermediate Filament Proteins / Q000096:biosynthesis; D050356:Lipid Metabolism; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D062793:Occludin; D010539:Permeability; D012697:Serine Endopeptidases / Q000235:genetics / Q000502:physiology*; D012868:Skin Abnormalities / Q000235:genetics / Q000473:pathology; D019108:Tight Junctions / Q000502:physiology; D000099271:Prostasin
chemical_list: D000091344:Filaggrin Proteins; D007381:Intermediate Filament Proteins; D008565:Membrane Proteins; D062793:Occludin; D012697:Serine Endopeptidases; D000099271:Prostasin; C568986:Ocln protein, mouse