Xue Xiaoxiao, Guo Yatao, Zhao Qianying, Li Yongwen, Rao Mi, Qi Wenjing, Shi Huijuan
Department of Dermatovenereology, the General Hospital of Ningxia Medical University, Yinchuan, 750004, People's Republic of China.
Dermatological Department, Baoji Central Hospital, Shaanxi, 721008, People's Republic of China.
J Inflamm Res. 2023 Mar 7;16:845-859. doi: 10.2147/JIR.S402535. eCollection 2023.
Psoriasis is a common, chronic, inflammatory, recurrent, immune-mediated skin disease. Oxymatrine is effective for treating moderate and severe psoriasis. Here, transcriptional changes in skin lesions before and after oxymatrine treatment of patients with psoriasis were identified using full-length transcriptome analysis and then compared with those of normal skin tissues.
Co-expression modules were constructed by combining the psoriasis area and severity index (PASI) score with weighted gene co-expression network analysis to explore the action mechanism of oxymatrine in improving clinical PASI. The expression of selected genes was verified using immunohistochemistry, quantitative real-time PCR, and Western blotting.
Kyoto Encyclopedia of Gene and Genome pathway analysis revealed that oxymatrine treatment reversed the abnormal pathways, with an improvement in lesions and a reduction in PASI scores. Gene Ontology (GO) analysis revealed that oxymatrine treatment led to altered GO terms being regulated with a decrease in the PASI score in patients. Therefore, oxymatrine treatment may improve the skin barrier, differentiation of keratinocytes, and alleviate abnormality of organelles such as desmosomes. Protein-protein interaction network interaction analysis revealed that the top five hub genes among many interrelated genes were , and , associated with the epidermal differentiation complex (EDC). EDC regulates keratinocyte differentiation. This result indicates that oxymatrine treatment can restore keratinocyte differentiation by regulating the expression of EDC-related genes.
Oxymatrine can improve erythema, scales, and other clinical symptoms of patients with psoriasis by regulating EDC-related genes and multiple pathways, thereby promoting the repair of epithelial tissue and maintaining the dynamic balance of skin keratosis.
银屑病是一种常见的慢性炎症性复发性免疫介导性皮肤病。氧化苦参碱对治疗中重度银屑病有效。在此,通过全长转录组分析确定银屑病患者氧化苦参碱治疗前后皮肤病变的转录变化,然后与正常皮肤组织的转录变化进行比较。
通过将银屑病面积和严重程度指数(PASI)评分与加权基因共表达网络分析相结合构建共表达模块,以探索氧化苦参碱改善临床PASI的作用机制。使用免疫组织化学、定量实时PCR和蛋白质印迹法验证所选基因的表达。
京都基因与基因组百科全书通路分析显示,氧化苦参碱治疗可逆转异常通路,使病变改善且PASI评分降低。基因本体论(GO)分析显示,氧化苦参碱治疗导致GO术语发生改变,且患者的PASI评分降低。因此,氧化苦参碱治疗可能改善皮肤屏障、角质形成细胞分化,并减轻桥粒等细胞器的异常。蛋白质-蛋白质相互作用网络相互作用分析显示,许多相互关联的基因中排名前五位的枢纽基因是 、 、 、 和 ,与表皮分化复合体(EDC)相关。EDC调节角质形成细胞分化。这一结果表明,氧化苦参碱治疗可通过调节EDC相关基因的表达来恢复角质形成细胞分化。
氧化苦参碱可通过调节EDC相关基因和多条通路改善银屑病患者的红斑、鳞屑等临床症状,从而促进上皮组织修复并维持皮肤角化的动态平衡。