Integrin-Linked Kinase Senses Hypoxia During Scar Angiogenesis

Abstract

Integrin-linked kinase (ILK) mediates signal transduction between cells and the extracellular matrix, regulating cell proliferation, migration, angiogenesis, and apoptosis. However, its roles in the formation of hypertrophic scars are not yet clear. In this study, we found that ILK was predominantly expressed on the microvascular endothelial cells and the epidermal basal cells of human hypertrophic scars. The proliferation, migration and angiogenesis of primary human scar microvascular endothelial cells (HSMECs) were significantly inhibited after ILK was silenced. The ILK inhibitor QLT0267 had the same effect of impeding angiogenesis in vitro by blocking ILK activity. Both siRNA and QLT0267 markedly decreased the expression of vascular endothelial growth factor, but not its receptors, such as human vascular endothelial cell growth factor receptor 1 or kinase insert domain-containing receptor. We also showed that the expression of ILK was enhanced by inducing mild hypoxia with CoCl2, but it was suppressed under serious hypoxia. Thus, ILK regulates HSMEC proliferation and angiogenesis and participates in the formation of hypertrophic scars, in which mild hypoxia may be the mechanism of action.