368 Epithelial-mesenchymal crosstalk communication promotes fibroblast activation and fibrosis in RDEB

Recessive dystrophic epidermolysis bullosa (RDEB) is a devastating progressive skin fragility disorder caused by deficiency in type VII collagen (C7) and favored pro-fibrotic pro-tumorigenic dermal stroma. RDEB has served as paradigmatic model of injury-driven fibrosis. Nevertheless, the contribution epithelial cells to fibrosis been scarcely addressed progression. To study effect keratinocytes on fibroblast activation fibrosis, we approached epithelial-mesenchymal communication an vitro surrogate model. Co-culture fibroblast-derived ECM promoted activated contractile phenotype fibroblasts. This was counteracted co-cultivating fibroblast-populated with healthy keratinocytes. Moreover, co-culture fibroblasts induced phenotype, contrary what observed when These results raise question whether differences are due C7 and, therefore, correction would be sufficient reverse their effect. Using genome editing tools, edited CRISPR/Cas9 technology restore expression. Interestingly, RDEB-edited partially reverted compared non-edited counterparts. However, minimum levels were not reached co-cultured suggests that promote beyond presence or absence there other factors influencing environment RDEB. preliminary finding may useful for development future therapeutic strategies, it plausible need adjuvant therapies, addition primary defect, achieve efficient curative approach.