Dermira Inc, Menlo Park, California, USA; Evommune Inc, Los Altos, California, USA.
Department of Dermatology, Stanford University School of Medicine, Redwood City, California, USA; Department of Dermatology, Taipei Medical University-Shuang Ho Hospital, New Taipei City, Taiwan; Department of Dermatology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.
J Invest Dermatol. 2021 Apr;141(4):800-809. doi: 10.1016/j.jid.2020.08.013. Epub 2020 Sep 14.
Papulopustular rosacea (PPR) is a chronic inflammatory skin disease with limited treatment options. Although multiple pathways have been described to be upregulated in PPR, a mechanistic understanding of the key drivers and interaction between pathways in PPR pathology is lacking. In this study, we utilized PPR skin biopsy explants to integrate both differentially expressed genes and differentially expressed proteins in paired nonlesional and lesional PPR tissue (n = 5 patients). The results of this study identified 92 differentially expressed genes and 20 differentially expressed proteins between paired PPR lesional and nonlesional explants. MAPK and TNF signaling pathways were the most significantly upregulated pathways in PPR lesional tissue and aligned with differently expressed proteins identified in this study. Both MAPK and TNF signaling pathways highlighted IL-1β as a potential central mediator for PPR pathogenesis. In support of this, stimulation of nonlesional explants with IL-1β resulted in transcriptomic and proteomic profiles similar to those of lesional PPR. In this integrative transcriptomic and quantitative protein analysis, we identified several inflammatory genes, proteins, and pathways, which may be contributing to PPR, as well as highlighted a potential role of IL-1β in driving inflammation in PPR.
脓疱性酒渣鼻（PPR）是一种慢性炎症性皮肤疾病，治疗选择有限。尽管已经描述了多种途径在 PPR 中上调，但对于 PPR 病理中关键驱动因素和途径之间的相互作用的机制理解仍有所欠缺。在这项研究中，我们利用 PPR 皮肤活检外植体，整合了配对的非病变和病变 PPR 组织中的差异表达基因和差异表达蛋白（n=5 名患者）。这项研究的结果确定了 92 个在配对 PPR 病变和非病变外植体之间差异表达的基因和 20 个差异表达的蛋白。MAPK 和 TNF 信号通路是 PPR 病变组织中上调最显著的通路，与本研究中鉴定的差异表达蛋白一致。MAPK 和 TNF 信号通路均强调了 IL-1β 作为 PPR 发病机制的潜在中心介质。支持这一点的是，用 IL-1β 刺激非病变外植体导致转录组和蛋白质组谱与病变 PPR 相似。在这项综合转录组和定量蛋白质分析中，我们鉴定了几个炎症基因、蛋白质和通路，它们可能与 PPR 有关，并强调了 IL-1β 在驱动 PPR 炎症中的潜在作用。
