title: Multiple roles of integrin-linked kinase in epidermal development, maturation and pigmentation revealed by molecular profiling.
abstract: Integrin-linked kinase (ILK) is an important scaffold protein that mediates a variety of cellular responses to integrin stimulation by extracellular matrix proteins. Mice with epidermis-restricted inactivation of the Ilk gene exhibit pleiotropic phenotypic defects, including impaired hair follicle morphogenesis, reduced epidermal adhesion to the basement membrane, compromised epidermal integrity, as well as wasting and failure to thrive leading to perinatal death. To better understand the underlying molecular mechanisms that cause such a broad range of alterations, we investigated the impact of Ilk gene inactivation on the epidermis transcriptome. Microarray analysis showed over 700 differentially regulated mRNAs encoding proteins involved in multiple aspects of epidermal function, including keratinocyte differentiation and barrier formation, inflammation, regeneration after injury, and fundamental epidermal developmental pathways. These studies also revealed potential effects on genes not previously implicated in ILK functions, including those important for melanocyte and melanoblast development and function, regulation of cytoskeletal dynamics, and homeobox genes. This study shows that ILK is a critical regulator of multiple aspects of epidermal function and homeostasis, and reveals the previously unreported involvement of ILK not only in epidermal differentiation and barrier formation, but also in melanocyte genesis and function.
authors.affiliation: Department of Physiology and Pharmacology, University of Western Ontario, and Children's Health Research Institute, London, Ontario, Canada.
authors.forename: David
authors.initials: D
authors.lastname: Judah
authors.forename: Alena
authors.initials: A
authors.lastname: Rudkouskaya
authors.forename: Ryan
authors.initials: R
authors.lastname: Wilson
authors.forename: David E
authors.initials: DE
authors.lastname: Carter
authors.forename: Lina
authors.initials: L
authors.lastname: Dagnino
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D000078404:Epidermal Cells; D004815:Epidermal Growth Factor / Q000378:metabolism; D004817:Epidermis / Q000254:growth & development* / Q000293:injuries / Q000378:metabolism*; D015971:Gene Expression Regulation, Enzymologic; D023281:Genomics; D018859:Hair Follicle / Q000378:metabolism; D053823:Hedgehog Proteins / Q000378:metabolism; D006706:Homeostasis; D015603:Keratinocytes / Q000166:cytology; D008544:Melanocytes / Q000378:metabolism; D051379:Mice; D010858:Pigmentation; D017346:Protein Serine-Threonine Kinases / Q000172:deficiency / Q000378:metabolism*; D011565:Psoriasis / Q000201:enzymology; D015398:Signal Transduction; D059467:Transcriptome; D051153:Wnt Proteins / Q000378:metabolism; D000099200:Scaffold Protein ILK
chemical_list: D004815:Epidermal Growth Factor; D053823:Hedgehog Proteins; D017346:Protein Serine-Threonine Kinases; D051153:Wnt Proteins; D000099200:Scaffold Protein ILK