Abstract：
BACKGROUND: Rosacea is an inflammatory skin disorder characterized by the release of inflammatory mediators from keratinocytes, which are thought to play a crucial role in its pathogenesis. Despite an incidence of approximately 5.5%, rosacea is associated with a poor quality of life. However, as the pathogenesis of rosacea remains enigmatic, treatment options are limited.
OBJECTIVE: To investigate the pathogenesis of rosacea and explore new therapeutic strategies.
METHODS: Transcriptome data from rosacea patients combined with immunohistochemical staining were used to investigate the activation of STAT3 in rosacea. The role of STAT3 activation in rosacea was subsequently explored by inhibiting STAT3 activation both in vivo and in vitro. The key molecules downstream of STAT3 activation were identified through data analysis and experiments. Dual-luciferase assay and ChIP-qPCR analysis were used to validate the direct binding of STAT3 to the IL-36G promoter. DARTS, in combination with experimental screening, was employed to identify effective drugs targeting STAT3 for rosacea treatment.
RESULTS: STAT3 signaling was hyperactivated in rosacea and served as a promoter of the keratinocyte-driven inflammatory response. Mechanistically, activated STAT3 directly bind to the IL-36G promoter region to amplify downstream inflammatory signals by promoting IL-36G transcription, and treatment with a neutralizing antibody (α-IL36γ) could mitigate rosacea-like inflammation. Notably, a natural plant extract (pogostone), which can interact with STAT3 directly to inhibit its activation and affect the STAT3/IL36G signaling pathway, was screened as a promising topical medication for rosacea treatment.
CONCLUSIONS: Our study revealed a pivotal role for STAT3/IL36G signaling in the development of rosacea, suggesting that targeting this pathway might be a potential strategy for rosacea treatment.
OBJECTIVE: To investigate the pathogenesis of rosacea and explore new therapeutic strategies.
METHODS: Transcriptome data from rosacea patients combined with immunohistochemical staining were used to investigate the activation of STAT3 in rosacea. The role of STAT3 activation in rosacea was subsequently explored by inhibiting STAT3 activation both in vivo and in vitro. The key molecules downstream of STAT3 activation were identified through data analysis and experiments. Dual-luciferase assay and ChIP-qPCR analysis were used to validate the direct binding of STAT3 to the IL-36G promoter. DARTS, in combination with experimental screening, was employed to identify effective drugs targeting STAT3 for rosacea treatment.
RESULTS: STAT3 signaling was hyperactivated in rosacea and served as a promoter of the keratinocyte-driven inflammatory response. Mechanistically, activated STAT3 directly bind to the IL-36G promoter region to amplify downstream inflammatory signals by promoting IL-36G transcription, and treatment with a neutralizing antibody (α-IL36γ) could mitigate rosacea-like inflammation. Notably, a natural plant extract (pogostone), which can interact with STAT3 directly to inhibit its activation and affect the STAT3/IL36G signaling pathway, was screened as a promising topical medication for rosacea treatment.
CONCLUSIONS: Our study revealed a pivotal role for STAT3/IL36G signaling in the development of rosacea, suggesting that targeting this pathway might be a potential strategy for rosacea treatment.
摘要：
背景：酒渣鼻是一种炎症性皮肤病，其特征是角质形成细胞释放炎症介质，被认为在其发病机理中起着至关重要的作用。尽管发病率约为5.5%，酒渣鼻与生活质量差有关。然而,由于酒渣鼻的发病机制仍然是神秘的，治疗方案有限。
目的：探讨酒渣鼻的发病机制，探索新的治疗策略。
方法：使用来自酒渣鼻患者的转录组数据结合免疫组织化学染色来研究酒渣鼻中STAT3的激活。随后通过在体内和体外抑制STAT3活化来探索STAT3活化在酒渣鼻中的作用。通过数据分析和实验鉴定了STAT3活化下游的关键分子。使用双荧光素酶测定和ChIP-qPCR分析来验证STAT3与IL-36G启动子的直接结合。达人,结合实验筛选，用于确定针对STAT3治疗酒渣鼻的有效药物。
结果：STAT3信号在酒渣鼻中过度激活，并作为角质形成细胞驱动的炎症反应的启动子。机械上,激活的STAT3直接与IL-36G启动子区结合，通过促进IL-36G转录来放大下游炎症信号，用中和抗体（α-IL36γ）治疗可以减轻酒渣鼻样炎症。值得注意的是,天然植物提取物（pogestone），能直接与STAT3相互作用,抑制其激活并影响STAT3/IL36G信号通路,被筛选为有希望的用于酒渣鼻治疗的局部药物。
结论：我们的研究揭示了STAT3/IL36G信号在酒渣鼻的发展中的关键作用，这表明靶向该途径可能是酒渣鼻治疗的潜在策略。
目的：探讨酒渣鼻的发病机制，探索新的治疗策略。
方法：使用来自酒渣鼻患者的转录组数据结合免疫组织化学染色来研究酒渣鼻中STAT3的激活。随后通过在体内和体外抑制STAT3活化来探索STAT3活化在酒渣鼻中的作用。通过数据分析和实验鉴定了STAT3活化下游的关键分子。使用双荧光素酶测定和ChIP-qPCR分析来验证STAT3与IL-36G启动子的直接结合。达人,结合实验筛选，用于确定针对STAT3治疗酒渣鼻的有效药物。
结果：STAT3信号在酒渣鼻中过度激活，并作为角质形成细胞驱动的炎症反应的启动子。机械上,激活的STAT3直接与IL-36G启动子区结合，通过促进IL-36G转录来放大下游炎症信号，用中和抗体（α-IL36γ）治疗可以减轻酒渣鼻样炎症。值得注意的是,天然植物提取物（pogestone），能直接与STAT3相互作用,抑制其激活并影响STAT3/IL36G信号通路,被筛选为有希望的用于酒渣鼻治疗的局部药物。
结论：我们的研究揭示了STAT3/IL36G信号在酒渣鼻的发展中的关键作用，这表明靶向该途径可能是酒渣鼻治疗的潜在策略。
