title: Epidermal activation of the small GTPase Rac1 in psoriasis pathogenesis.
abstract: The small GTPase Ras-related C3 botulinum toxin substrate 1 (RAC1) plays a central role in skin homeostasis, including barrier function, wound healing and inflammatory responses. Psoriasis is a common skin disease characterized by deregulation of these functions, and affected skin exhibit keratinocyte hyperproliferation, inflammation and immune cell infiltration. Although psoriasis is often triggered by environmental stimulus, there is a strong genetic association with genes expressed in both immune cells and keratinocytes, of which several are linked to Rac1 signaling. Rac1 is highly active in human psoriatic lesional skin and keratinocytes, and keratinocyte-specific overexpression of an activated mutant of Rac1, Rac1V12, in a transgenic mouse model closely mimics the presentation of human psoriasis. Both Rac1 activation in keratinocytes and immune derived stimulus are required to drive psoriasiform signaling in transgenic mouse and human xenograft models of psoriasis. Therefore, understanding how increased Rac1 activation in psoriatic epidermis is regulated is central to understanding how the abnormal crosstalk between keratinocytes and immune cells is maintained.
authors.affiliation: a Program in Epithelial Biology , Stanford University School of Medicine , Stanford , CA , USA.
authors.forename: Mårten C G
authors.initials: MCG
authors.lastname: Winge
authors.affiliation: a Program in Epithelial Biology , Stanford University School of Medicine , Stanford , CA , USA.|b Dermatology Service , Veterans Affairs Medical Center , Palo Alto , CA , USA.
authors.forename: M Peter
authors.initials: MP
authors.lastname: Marinkovich
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D004195:Disease Models, Animal; D004789:Enzyme Activation / Q000235:genetics; D004817:Epidermis / Q000196:embryology* / Q000473:pathology; D006801:Humans; D015603:Keratinocytes / Q000201:enzymology* / Q000473:pathology; D051379:Mice; D008822:Mice, Transgenic; D009154:Mutation; D011565:Psoriasis / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D020830:rac1 GTP-Binding Protein / Q000235:genetics / Q000378:metabolism*
chemical_list: C107953:RAC1 protein, human; D020830:rac1 GTP-Binding Protein
keywords: Rac1; crosstalk; epidermis-immune; keratinocyte; psoriasis