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

TL;DR

This study shows that a protein called ILK is crucial for how skin cells respond to mechanical stress, affecting cell structure and gene activity.

Contribution

The study reveals new roles for ILK in mechanotransduction in keratinocytes, including effects on cytoskeleton and YAP activity.

Findings

ILK-deficient keratinocytes show disrupted Collagen XVII and reduced YAP nuclear localization.

Mechanical strain induces actin rearrangements and YAP activation in ILK+ but not ILK-KO cells.

miRNA expression changes in response to strain differ between ILK+ and ILK-KO cells.

Abstract

Mechanical signals play key roles in the regulation of epidermal homeostasis and regeneration after injury. Integrins are key components of focal adhesions, and these complexes are major contributors to mechanotransduction. In keratinocytes, integrin-linked kinase (ILK) modulates essential processes for epidermal homeostasis and wound repair. However, its functions in the transduction of mechanical stimuli have remained virtually unexplored. In this study, we characterized epidermal tissues and primary keratinocytes from mice with epidermis-restricted inactivation of the Ilk gene (ILK-KO). ILK-deficient epidermis exhibits abnormalities in key components of mechanotransduction cascades, including disruptions in hemidesmosomal Collagen XVII immunoreactivity at the dermal–epidermal junction, and marked reduction in the nuclear localization of the mechanosensitive transcriptional regulator YAP. In wild-type (ILK+), but not in ILK-KO-cultured keratinocytes, exposure to cyclic bidirectional strain induced marked F-actin cytoskeletal rearrangements, characterized by the assembly of thick cortical actin bundles and stress fibers, as well as YAP nuclear translocation and transcriptional activity. Exposure to mechanical strain was additionally accompanied by differential changes in miRNA expression between ILK+ and ILK-KO cells. These findings reveal multiple and previously unappreciated key regulatory roles for ILK in epidermal keratinocyte responses to mechanical signals.

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