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银屑病的靶向性小干扰RNA疗法:将临床前潜力转化为临床治疗方法

Targeted siRNA Therapy for Psoriasis: Translating Preclinical Potential into Clinical Treatments.

作者信息

Zhao Fuyu, Zhao Jianan, Wei Kai, Jiang Ping, Shi Yiming, Chang Cen, Zheng Yixin, Shan Yu, Li Yunshen, He Bingheng, Zhou Mi, Liu Jia, Li Li, Guo Shicheng, He Dongyi

机构信息

Department of Rheumatology, Shanghai Guanghua Hospital of Integrative Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, People's Republic of China.

Guanghua Clinical Medical College, Shanghai University of Traditional Chinese Medicine, Shanghai, People's Republic of China.

出版信息

Immunotargets Ther. 2024 May 16;13:259-271. doi: 10.2147/ITT.S458800. eCollection 2024.

Abstract

Psoriasis is a chronic inflammatory skin disease characterized by the excessive proliferation of keratinocytes and heightened immune activation. Targeting pathogenic genes through small interfering RNA (siRNA) therapy represents a promising strategy for the treatment of psoriasis. This mini-review provides a comprehensive summary of siRNA research targeting the pathogenesis of psoriasis, covering aspects such as keratinocyte function, inflammatory cell roles, preclinical animal studies, and siRNA delivery mechanisms. It details recent advancements in RNA interference that modulate key factors including keratinocyte proliferation (Fibroblast Growth Factor Receptor 2, ), apoptosis (Interferon Alpha Inducible Protein 6, ), differentiation (Grainyhead Like Transcription Factor 2, ), and angiogenesis (Vascular Endothelial Growth Factor, ); immune cell infiltration and inflammation (Tumor Necrosis Factor-Alpha, ; Interleukin-17, ); and signaling pathways (, Nuclear Factor Kappa B, ) that govern immunopathology. Despite significant advances in siRNA-targeted treatments for psoriasis, several challenges persist. Continued scientific developments promise the creation of more effective and safer siRNA medications, potentially enhancing the quality of life for psoriasis patients and revolutionizing treatments for other diseases. This article focuses on the most recent research advancements in targeting the pathogenesis of psoriasis with siRNA and explores its future therapeutic prospects.

摘要

银屑病是一种慢性炎症性皮肤病,其特征为角质形成细胞过度增殖和免疫激活增强。通过小干扰RNA(siRNA)疗法靶向致病基因是治疗银屑病的一种有前景的策略。本综述全面总结了针对银屑病发病机制的siRNA研究,涵盖角质形成细胞功能、炎症细胞作用、临床前动物研究以及siRNA递送机制等方面。它详细介绍了RNA干扰的最新进展,这些进展调节了包括角质形成细胞增殖(成纤维细胞生长因子受体2)、凋亡(干扰素α诱导蛋白6)、分化(颗粒头样转录因子2)和血管生成(血管内皮生长因子)等关键因子;免疫细胞浸润和炎症(肿瘤坏死因子-α;白细胞介素-17);以及控制免疫病理学的信号通路(核因子κB)。尽管针对银屑病的siRNA靶向治疗取得了重大进展,但仍存在一些挑战。持续的科学发展有望创造出更有效、更安全的siRNA药物,可能提高银屑病患者的生活质量,并彻底改变其他疾病的治疗方法。本文重点介绍了用siRNA靶向银屑病发病机制的最新研究进展,并探讨了其未来的治疗前景。

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