Abstract
Men often presented with higher severity of psoriasis than women, but the underlying reasons are still unclear. In this study, we evaluate proteomic differences in psoriatic lesions between men and women with moderate-to-severe psoriasis and explore possible protective and risk proteins using data-independent acquisition mass spectrometry (DIA-MS) and verified by 4D-parallel reaction monitoring (4D-PRM). 416 differentially expressed proteins (DEPs) were identified between two groups. Among them, 94 proteins were upregulated, while 322 were down-regulated. Some DEPs were enriched to pathways associated with psoriasis, such as the IL − 17 signalling pathway, T cell receptor signalling pathway, Th17 cell differentiation, Oxidative phosphorylation, PI3K − Akt signalling pathway, and MAPK signalling pathway; meanwhile, numerous pathways associated with infection. Nine DEPs (KRT36, KRT13, KRT15, SHC1, GNAI1, SRC, HSPA6, HSPA1L, and HSP90AB4P) were involved in the estrogen pathway, which was predicted to be activated in males. Through Ingenuity pathway Analysis (IPA), our data also identified three upstream regulators (TNF, KRAS, TGFB1). 4D-PRM suggested that HMGB2 and PML were upregulated, while LAMTOR3 was downregulated in male group compared to female one. Our study suggests that sex may influence protein changes in psoriasis, pathogenesis and disease severity. Targeting these molecules may improve the severity and therapeutic efficacy of psoriasis.