The potential role for Interferon regulatory factor 6 in keratinocyte adhesion and/or migration

Abstract

Mutations in Interferon Regulatory Factor (IRF6) cause two orofacial clefting syndromes, Van der Woude (VWS) and Popliteal Pterygium (PPS). In addition to an oral defect, recent data show that VWS patients are more likely to have wound complications after corrective cleft surgery than patients with isolated cleft. Thus we hypothesize that Irf6 is critical to wound closure. To test this, we used keratinocytes from Irf6 null mice. We created in vitro scratches and observed a significant delay in scratch closure. To determine the cause of delay, we examined the cellular structure of Irf6−/− keratinocytes by staining for filamentous actin and found that these cells have more stress fibers. In addition, we examined cellular adhesion by staining Irf6−/− keratinocytes for E‐cadherin and vinculin. We found that these cells form junctions, but cell‐cell contacts appear in an abnormal pattern, and there appear to be more focal adhesions. Finally, we analyzed proliferation of Irf6−/− keratinocytes and found no deficiency. Together, our data suggests Irf6−/− keratinocytes exhibit characteristics of less motile cells. Thus, we speculate that the defect in Irf6−/− keratinocyte scratch closure is due to aberrant migration and/or adhesion, and that cellular proliferation is not inhibitory to closure. Broadly, these data suggest that Irf6 is necessary for events critical to proper cutaneous wound healing.Grant Funding Source: NIH‐NIAMS AR 055313