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.
Highlights
The skin is the largest organ of the body, and its upper layer, the epidermis, is a barrier that fulfills critical protective and homeostatic functions
Transcriptional profiling of Integrin-linked kinase (ILK)-deficient epidermis To define the molecular role of ILK in epidermal function, we analyzed gene expression profiles of ILK-deficient and ILKexpressing epidermis
We prepared protein lysates from ILK-deficient (K14Cre; Ilkf/f) and ILK-expressing (K14Cre; Ilkf/+) epidermis from 3 day-old mice, because at this age most animals are still viable, in spite of their severe epidermal alterations [9]. These experiments showed that K14Cre; Ilkf/f epidermis expresses ILK protein levels that are #12% of those found in epidermal tissues from K14Cre; Ilkf/+ mice (Fig. 1A), demonstrating the high efficiency of Ilk gene inactivation in our model
Summary
The skin is the largest organ of the body, and its upper layer, the epidermis, is a barrier that fulfills critical protective and homeostatic functions. These experiments showed that K14Cre; Ilkf/f epidermis expresses ILK protein levels that are #12% of those found in epidermal tissues from K14Cre; Ilkf/+ mice (Fig. 1A), demonstrating the high efficiency of Ilk gene inactivation in our model. Reduced expression of hair follicle genes in ILK-deficient epidermis
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