Zhou Lei, Zhong Yun, Wang Yaling, Deng Zhili, Huang Yingxue, Wang Qian, Xie Hongfu, Zhang Yiya, 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.
Front Pharmacol. 2023 Mar 1;14:1092473. doi: 10.3389/fphar.2023.1092473. eCollection 2023.
Rosacea is a common facial skin inflammatory disease featured by hyperactivation of mTORC1 signaling in the epidermis. Due to unclear pathogenesis, the effective treatment options for rosacea remain limited. Weighted gene co-expression network analysis (WGCNA) analyzed the relationship between epidermis autophagy and mTOR pathways in rosacea, and further demonstrated it through immunofluorescence and qPCR analysis. A potential therapeutic agent for rosacea was predicted based on the key genes of the WGCNA module. and experiments were conducted to verify its therapeutic role. Drug-target prediction (TargetNet, Swiss, and Tcmsp) and molecular docking offered potential pharmacological targets. WGCNA showed that epidermis autophagy was related to the activation of mTOR pathways in rosacea. Next, autophagy was downregulated in the epidermis of rosacea, which was regulated by mTOR. In addition, the experiment demonstrated that autophagy induction could be an effective treatment strategy for rosacea. Subsequently, based on the key genes of the WGCNA module, epigallocatechin-3-gallate (EGCG) was predicted as a potential therapeutic agent for rosacea. Furthermore, the therapeutic role of EGCG on rosacea was confirmed and . Finally, drug-target prediction and molecular docking revealed that AKT1/MAPK1/MMP9 could be the pharmacological targets of EGCG in rosacea. Collectively, our findings revealed the vital role of autophagy in rosacea and identified that EGCG, as a therapeutic agent for rosacea, attenuated rosacea-like inflammation inducing autophagy in keratinocytes.
酒渣鼻是一种常见的面部皮肤炎症性疾病,其特征是表皮中mTORC1信号过度激活。由于发病机制尚不清楚,酒渣鼻的有效治疗选择仍然有限。加权基因共表达网络分析(WGCNA)分析了酒渣鼻表皮自噬与mTOR通路之间的关系,并通过免疫荧光和qPCR分析进一步证实了这一点。基于WGCNA模块的关键基因预测了一种潜在的酒渣鼻治疗药物,并进行了实验以验证其治疗作用。药物靶点预测(TargetNet、Swiss和Tcmsp)和分子对接提供了潜在的药理学靶点。WGCNA表明,表皮自噬与酒渣鼻mTOR通路的激活有关。接下来,酒渣鼻表皮中的自噬被下调,这是由mTOR调节的。此外,实验表明诱导自噬可能是治疗酒渣鼻的有效策略。随后,基于WGCNA模块的关键基因,表没食子儿茶素-3-没食子酸酯(EGCG)被预测为酒渣鼻的潜在治疗药物。此外,EGCG对酒渣鼻的治疗作用得到了证实。最后,药物靶点预测和分子对接显示,AKT1/MAPK1/MMP9可能是EGCG在酒渣鼻治疗中的药理学靶点。总之,我们的研究结果揭示了自噬在酒渣鼻中的重要作用,并确定EGCG作为酒渣鼻的治疗药物,通过诱导角质形成细胞自噬减轻了酒渣鼻样炎症。