title: Systematic identification and characterization of novel human skin-associated genes encoding membrane and secreted proteins.
abstract: Through bioinformatics analyses of a human gene expression database representing 105 different tissues and cell types, we identified 687 skin-associated genes that are selectively and highly expressed in human skin. Over 50 of these represent uncharacterized genes not previously associated with skin and include a subset that encode novel secreted and plasma membrane proteins. The high levels of skin-associated expression for eight of these novel therapeutic target genes were confirmed by semi-quantitative real time PCR, western blot and immunohistochemical analyses of normal skin and skin-derived cell lines. Four of these are expressed specifically by epidermal keratinocytes; two that encode G-protein-coupled receptors (GPR87 and GPR115), and two that encode secreted proteins (WFDC5 and SERPINB7). Further analyses using cytokine-activated and terminally differentiated human primary keratinocytes or a panel of common inflammatory, autoimmune or malignant skin diseases revealed distinct patterns of regulation as well as disease associations that point to important roles in cutaneous homeostasis and disease. Some of these novel uncharacterized skin genes may represent potential biomarkers or drug targets for the development of future diagnostics or therapeutics.
authors.affiliation: Department of Dermatology, University of Düsseldorf, Düsseldorf, Germany.
authors.forename: Peter Arne
authors.initials: PA
authors.lastname: Gerber
authors.forename: Peter
authors.initials: P
authors.lastname: Hevezi
authors.forename: Bettina Alexandra
authors.initials: BA
authors.lastname: Buhren
authors.forename: Cynthia
authors.initials: C
authors.lastname: Martinez
authors.forename: Holger
authors.initials: H
authors.lastname: Schrumpf
authors.forename: Marcia
authors.initials: M
authors.lastname: Gasis
authors.forename: Susanne
authors.initials: S
authors.lastname: Grether-Beck
authors.forename: Jean
authors.initials: J
authors.lastname: Krutmann
authors.forename: Bernhard
authors.initials: B
authors.lastname: Homey
authors.forename: Albert
authors.initials: A
authors.lastname: Zlotnik
mesh_terms: D015415:Biomarkers / Q000378:metabolism; D002478:Cells, Cultured; D005260:Female; D006801:Humans; D007375:Interleukin-1 / Q000235:genetics / Q000378:metabolism; D015603:Keratinocytes / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D008894:Milk Proteins / Q000235:genetics / Q000378:metabolism*; D058977:Molecular Sequence Annotation; D009928:Organ Specificity; D061251:Primary Cell Culture; D049368:Receptors, Lysophosphatidic Acid / Q000235:genetics / Q000378:metabolism*; D015843:Serpins / Q000235:genetics / Q000378:metabolism*; D012867:Skin / Q000378:metabolism* / Q000473:pathology; D012871:Skin Diseases / Q000378:metabolism / Q000473:pathology; D059467:Transcriptome
chemical_list: D015415:Biomarkers; C526276:GPR87 protein, human; C508587:IL37 protein, human; D007375:Interleukin-1; D008565:Membrane Proteins; D008894:Milk Proteins; D049368:Receptors, Lysophosphatidic Acid; C114170:SERPINB7 protein, human; D015843:Serpins; C581204:TMEM45A protein, human; C024471:whey acidic proteins