ALA光动力激活OLR1-NF-κB正反馈环路抑制痤疮皮脂过度分泌的机制研究

抑制皮脂过度分泌是ALA光动力治疗重度痤疮的关键起效途径，但机制尚未阐明。本课题率先关注到ALA光动力抑制皮脂过度分泌是一种“长期效应”，应用生物信息学手段分析ALA光动力治疗前、后重度痤疮临床样本的基因表达谱芯片，发现治疗后痤疮组织OLR1表达显著上调。并通过细胞实验证实ALA光动力上调OLR1表达与抑制皮脂分泌相关。结合最新研究显示OLR1能与NF-κB形成正反馈环路，正反馈环路的形成有利于发挥长期的信号调控作用，本课题提出ALA光动力活化OLR1-NF-κB正反馈环路，并通过上调β-catenin抑制皮脂分泌相关基因，发挥抑制皮脂过度分泌“长期效应”这一科学假说。拟进一步应用临床样本、金黄地鼠痤疮模型、皮脂腺细胞痤疮模型从体内、细胞与分子水平，探索OLR1-NF-κB正反馈环路的活化机制及其抑制皮脂过度分泌的关键信号通路。为临床ALA光动力治疗重度痤疮提供新的理论依据及优化新策略。

Inhibition of sebum hypersecretion is the key effect of 5-aminolevulinic acid photodynamic therapy (ALA-PDT) in the treatment of severe acne vulgaris. However, the mechanism of this effect hasn’t been elucidated. This project is the first to pay attention to the fact that the inhibition of ALA-PDT for sebum hypersecretion is a "long-term effect". The bioinformatics method was used to analyze the gene expression profile chip of clinical samples of severe acne vulgaris before and after ALA-PDT. It was found that the expression of OLR1 in skin lesion tissue was significantly up-regulated after treatment. And it was further confirmed by cell experiments that the up-regulation of OLR1 expression caused by ALA-PDT is associated with inhibition of sebum hypersecretion. Based on the latest researches which show OLR1 can form a positive feedback loop with NF-κB and the formation of the positive feedback loop is conducive to the long-term signal regulation, this project proposes a scientific hypothesis that ALA-PDT activates the OLR1-NF-κB positive feedback loop and inhibits sebum secretion-related genes by up-regulating β-catenin, exerting the "long-term effect" on the inhibition of sebum hypersecretion. To confirm this scientific hypothesis, the clinical samples, golden hamster acne models, and sebaceous gland cell acne models will be used to explore the activation mechanism of OLR1-NF-κB positive feedback loop and its key signaling pathways for the inhibition of sebum hypersecretion from in vivo, cellular and molecular levels. This project may provide a new theoretical basis and a new optimization strategy for clinical ALA-PDT in the treatment of severe acne vulgaris.