title: Proteases and proteomics: cutting to the core of human skin pathologies.
abstract: Preserving the integrity of the skin's outermost layer (the epidermis) is vital for humans to thrive in hostile surroundings. Covering the entire body, the epidermis forms a thin but impenetrable cellular cordon that repels external assaults and blocks escape of water and electrolytes from within. This structure exists in a perpetual state of regeneration where the production of new cellular subunits at the base of the epidermis is offset by the release of terminally differentiated corneocytes from the surface. It is becoming increasingly clear that proteases hold vital roles in assembling and maintaining the epidermal barrier. More than 30 proteases are expressed by keratinocytes or infiltrating immune cells and the activity of each must be maintained within narrow limits and confined to the correct time and place. Accordingly, over- or under-exertion of proteolytic activity is a common factor in a multitude of skin disorders that range in severity from relatively mild to life-threatening. This review explores the current state of knowledge on the involvement of proteases in skin diseases and the latest findings from proteomic and transcriptomic studies focused on uncovering novel (patho)physiological roles for these enzymes.
authors.affiliation: Université Paris Descartes - Sorbonne Paris Cité, Paris, France; INSERM UMR 1163, Laboratory of Genetic Skin Diseases, Imagine Institute, Paris, France; Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Australia.
authors.forename: Simon J
authors.initials: SJ
authors.lastname: de Veer
authors.forename: Laetitia
authors.initials: L
authors.lastname: Furio
authors.forename: Jonathan M
authors.initials: JM
authors.lastname: Harris
authors.forename: Alain
authors.initials: A
authors.lastname: Hovnanian
mesh_terms: D000818:Animals; D020869:Gene Expression Profiling; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D010447:Peptide Hydrolases / Q000235:genetics / Q000378:metabolism*; D011480:Protease Inhibitors / Q000378:metabolism; D040901:Proteomics / Q000379:methods*; D012871:Skin Diseases / Q000201:enzymology* / Q000473:pathology
chemical_list: D011480:Protease Inhibitors; D010447:Peptide Hydrolases
keywords: Epidermis; Inflammation; Keratinocyte; Permeability barrier; Therapeutic target