title: Proteases: common culprits in human skin disorders.
abstract: Recent findings from the clinic and the laboratory have transformed the way proteases and their inhibitors are perceived in the outermost layer of the skin, the epidermis. It now appears that an integrated proteolytic network operates within the epidermis, comprising more than 30 enzymes that carry out a growing list of essential functions. Equally, defective regulation or execution of protease-mediated processes is emerging as a key contributor to diverse human skin pathologies, and in recent years the number of diseases attributable to aberrant proteolytic activity has more than doubled. Here, we survey the different roles of proteases in epidermal homeostasis (from processing enzymes to signalling molecules) and explore the spectrum of rare and common human skin disorders where proteolytic pathways are dysregulated.
authors.affiliation: INSERM, U781, 75743 Cedex 15, Paris, France; Université Paris Descartes and Institute Imagine, 75743 Cedex 15, Paris, France; Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, QLD 4059, Australia.
authors.forename: Simon J
authors.initials: SJ
authors.lastname: de Veer
authors.affiliation: INSERM, U781, 75743 Cedex 15, Paris, France; Université Paris Descartes and Institute Imagine, 75743 Cedex 15, Paris, France.
authors.forename: Laetitia
authors.initials: L
authors.lastname: Furio
authors.affiliation: Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, QLD 4059, Australia.
authors.forename: Jonathan M
authors.initials: JM
authors.lastname: Harris
authors.affiliation: INSERM, U781, 75743 Cedex 15, Paris, France; Université Paris Descartes and Institute Imagine, 75743 Cedex 15, Paris, France; Department of Genetics, CHU Necker-Enfants Malades, 75743 Cedex 15, Paris, France. Electronic address: alain.hovnanian@inserm.fr.
authors.forename: Alain
authors.initials: A
authors.lastname: Hovnanian
mesh_terms: D002454:Cell Differentiation; D004817:Epidermis / Q000201:enzymology; D006706:Homeostasis; D006801:Humans; D015603:Keratinocytes / Q000378:metabolism; D010447:Peptide Hydrolases / Q000378:metabolism*; D011480:Protease Inhibitors / Q000378:metabolism; D059748:Proteolysis; D012867:Skin / Q000201:enzymology / Q000473:pathology; D012871:Skin Diseases / Q000201:enzymology* / Q000473:pathology
chemical_list: D011480:Protease Inhibitors; D010447:Peptide Hydrolases
keywords: allergy; differentiation; epidermis; homeostasis; inflammation; keratinocyte