598 The polyamines spermidine and spermine are essential regulators of epidermal differentiation and cell migration during wound healing

The polyamines putrescine, spermidine and spermine are ubiquitously expressed cations that essential for normal cellular function. AMD1 is a key, rate limiting enzyme drives the conversion of putrescine to thus can change ratios three polyamines. polyamines, specifically spermine, show dramatic reduction in levels aged skin yet their role within not well understood. purpose this study was examine barrier formation wound healing. We regulation ratio critical polyamine regulator mediates change. Knockdown or inhibition 2D 3D models inhibits epidermal differentiation. This be fully rescued with supplementation. RNA sequencing analysis on inhibited cells confirms key upstream driver further demonstrate an promoting cell migration during strongly up-regulated edge keratinocytes ex vivo wounded human biopsies scratched, cultured keratinocytes. Knock-down delayed closure suggesting high required migration. have identified HuR as binding protein functions downstream wounding. promote stabilization mRNAs whose products drive propose fine-tuning control keratinocyte differentiation important targets multiple pathways