Essential Role of Integrin-Linked Kinase in Keratinocyte Responses to Mechanical Strain

This study investigated how integrin-linked kinase (ILK), a focal-adhesion scaffold protein, regulates epidermal keratinocyte mechanotransduction in vivo and in vitro. Using mice with epidermis-restricted Ilk inactivation (ILK-KO), the authors found skin fragility with dermal–epidermal microblistering and disrupted hemidesmosomal/adhesion signaling (including discontinuous Collagen XVII at the dermal–epidermal junction and altered Rac1 immunoreactivity). A major mechanotransduction phenotype was reduced nuclear localization of the mechanosensitive transcriptional regulator YAP in ILK-KO epidermis versus controls. In primary keratinocyte cultures, cyclic bidirectional strain induced robust focal-adhesion remodeling, F-actin cytoskeletal reorganization (thick actin bundles/stress fibers), and strong YAP nuclear translocation in ILK+ cells, but these responses were markedly impaired in ILK-KO keratinocytes. Mechanical strain increased expression of canonical YAP target genes (Ctgf, Cyr61, Csf1) only in ILK+ cells. Finally, microarray profiling and RT-qPCR validation showed that cyclic strain induces a mechanosensitive miRNA program in ILK+ keratinocytes that is substantially altered/blunted by ILK loss. Collectively, the work positions ILK as a key upstream node linking integrin adhesion complexes to F-actin remodeling, YAP-dependent transcription, and strain-responsive miRNA regulation in epidermal keratinocytes—mechanisms relevant to skin homeostasis and wound repair.