Lnc-AGXT2L1/miR-484/ERRα轴调控角质形成细胞糖酵解及能量代谢在银屑病中的作用和机制

银屑病病因不明、机制不清，严重影响患者生活质量。角质形成细胞（keratinocyte，KC）异常活化是银屑病发病核心环节，调控KC能量代谢的关键信号分子有可能成为潜在治疗靶点。研究发现ERRα在调控糖酵解和能量代谢中发挥着重要作用。我们前期研究证实银屑病患者皮损的lncRNA-AGXT2L1及雌激素相关受体α（ERRα）表达水平显著升高；结合生物信息学分析，我们提出假说lncRNA-AGXT2L1特异性靶向miR-484，调控ERRα的3’-UTR区域，通过调控KC糖酵解和能量代谢引起KC异常活化参与银屑病发生发展。本课题拟从临床组织标本、细胞水平、小鼠体内模型三个层面，探究Lnc-AGXT2L1/miR-484/ERRα轴调控银屑病KC糖酵解及能量代谢的具体分子机制。本研究将进一步丰富银屑病发病的分子机制，明确将Lnc-AGXT2L1作为治疗靶点干预银屑病进展的有效性和安全性。

The cause of psoriasis is unknown and effective treatments are lacking, which seriously affects the quality of work and life of patients. Keratinocyte (KC) abnormal activation and proliferation is the core link of psoriasis. In the process of psoriasis, key signal molecules which regulate keratinocyte (KC) glycolysis and energy metabolism may become potential therapeutic targets.Our research confirmed that the expression levels of lncRNA-AGXT2L1 and estrogen-related receptor α (ERRα) in the lesion of psoriasis patients group increased significantly; ERRα promotes the progression of psoriasis by regulating KC glycolysis and energy metabolism.Combining with bioinformatics analysis results, we further hypothesized that lncRNA-AGXT2L1 specifically targets miR-484,which regulates the 3'-UTR region of ERRα, to regulate the occurrence and progression of psoriasis.This project intends to explore the specific molecular mechanisms of the Lnc-AGXT2L1 / miR-484 / ERRα axis regulating the glycolysis and energy metabolism of KC in psoriasis from three levels of clinical tissue specimens, mouse in vivo models and cellular levels.This study will further enrich the molecular mechanism of the pathogenesis of psoriasis and make it clear that Lnc-AGXT2L1 is a therapeutic target with effectiveness and safety to intervene the progression of psoriasis.