370 Role of proliferation and mechanostructural signaling in pemphigus vulgaris

Previous studies have shown that mechanostructural properties of keratinocytes are altered upon anti-Dsg3 antibody treatment. However, the involvement these changes in pathogenesis pemphigus vulgaris (PV) has not been fully elucidated. In this study, we first utilized a keratinocyte dissociation assay (KDA) to via pharmacological modulators and knock-out cells, whether transcription, actomyosin contractility, E-cadherin, cell proliferation required for loss cohesion. Then performed flow cytometric assays on BrdU incorporation into treated with AK23 (anti-Dsg3) uncover effect proliferation. Bulk RNA-sequencing was 2D cultures primary human epidermal longitudinally experimental antibodies, or PX43 (anti-Dsg1/3), elucidate transcriptional involved disease-induced contraction KDA results suggest proliferative mechanisms, contraction, regulation AK23-induced fragmentation, while E-cadherin involved. Flow analysis at 24 hours confirmed AK23-treated were more compared control antibody-treated cells. Consistent abovementioned findings, RNA-seq revealed modulation replication, cycle, WNT, Rho GTPases, apoptosis-related genes over time.