040 Vildagliptin administration alters mouse skin proteome

Bullous pemphigoid (BP) is a subcutaneous blistering skin disease in which IgG autoantibodies are formed against the hemidesmosomal protein BP180. Epidemiological studies have revealed strong association between an increased risk of BP and use dipeptidyl peptidase 4 inhibitors (DPP4i/gliptins), especially vildagliptin. We performed proteomic study on vildagliptin-exposed mice to reveal factors for development DPP4i-associated BP. administered vildagliptin via drinking water (control group, n = 5, treatment group 6) three months used minimum two-dimensional difference gel electrophoresis (2D-DIGE) effects proteome. identified spots with mass spectrometry (MS) validated results using label-free shotgun MS, immunoblotting (IB), qPCR, immunohistochemistry (IHC). detected upregulation beta-actin (treatment/ctrl ratio 1.76) moesin (1.74) vildagliptin-treated 2D-DIGE IB, increase galectin-1 (4.18) MS. A downregulation DPP4 (0.83) was IB. IHC showed that decreased staining moesin, galectin-1, epidermal keratinocytes dermal fibroblasts. In addition, IB decrease BP180 (0.68) mice. The discrepancies may arouse from partition by solubility former and/or epitope masking/modification latter. morphology normal. No differences were observed mRNA level qPCR analysis. conclude administration alters mouse cutaneous expression beta-actin, DPP4, These proteins participate e.g., cytoskeleton-cell membrane interaction, T-lymphocyte regulation, could role breakage immunotolerance