Meng Xin, Zhong Yun, Kuang Xuyuan, Zhang Yiya, Yang Li, Cai Yisheng, Wang Fan, He Fanping, Xie Hongfu, Wang Ben, Li Ji
Department of Dermatology, Xiangya Hospital, Central South University, Changsha, China; Hunan Key Laboratory of Aging Biology, Xiangya Hospital, Central South University, Changsha, China.
Department of Hyperbaric Oxygen, Xiangya Hospital, Central South University, Jiangxi, China; Department of Hyperbaric Oxygen, Xiangya Hospital, Central South University, Changsha, China.
J Adv Res. 2025 May;71:429-440. doi: 10.1016/j.jare.2024.06.013. Epub 2024 Jun 22.
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.
To investigate the pathogenesis of rosacea and explore new therapeutic strategies.
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.
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.
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.
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，这些介质被认为在其发病机制中起关键作用。尽管发病率约为5.5%，但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不明，治疗选择有限。
研究酒渣鼻的发病机制并探索新的治疗策略。
结合酒渣鼻患者的转录组数据和免疫组化染色来研究酒渣鼻中信号转导及转录激活因子3（STAT3）的激活情况。随后通过体内和体外抑制STAT3激活来探讨其在酒渣鼻发病中的作用。通过数据分析和实验确定STAT3激活下游的关键分子。采用双荧光素酶报告基因检测和染色质免疫沉淀-定量聚合酶链反应（ChIP-qPCR）分析来验证STAT3与白细胞介素36G（IL-36G）启动子的直接结合。采用药物亲和反应靶标稳定性（DARTS）结合实验筛选来鉴定针对STAT3治疗酒渣鼻的有效药物。
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促进因子。机制上，激活的STAT3直接结合到IL-36G启动子区域，通过促进IL-36G转录来放大下游炎症信号，用中和抗体（α-IL36γ）治疗可减轻酒渣鼻样炎症。值得注意的是，一种天然植物提取物（广藿香酮）可直接与STAT3相互作用以抑制其激活并影响STAT3/IL36G信号通路，经筛选它是一种有前景的酒渣鼻局部治疗药物。
我们的研究揭示了STAT3/IL36G信号在酒渣鼻发生发展中的关键作用，表明靶向该通路可能是酒渣鼻治疗的潜在策略。
