Li Han, Wu Qi-Yang, Teng Xu-Heng, Li Zhi-Peng, Zhu Meng-Ting, Gu Chao-Jie, Chen Ben-Jia, Xie Qi-Qi, LuO Xin-Jing
Taizhou University, Taizhou, Zhejiang, China.
Cent Eur J Immunol. 2023;48(4):338-345. doi: 10.5114/ceji.2023.134217. Epub 2024 Jan 8.
Rheumatoid arthritis (RA) is a prevalent autoimmune disease that involves the overgrowth and inflammation of synovial tissue, leading to the degeneration and impairment of joints. In recent years, numerous studies have shown a close relationship between the hypoxic microenvironment in joints and the occurrence and progression of RA. The main cause of the pathological changes in RA is widely believed to be the abnormal expression of hypoxia-inducible factor-1 (HIF-1) in joints. This paper describes and illustrates the structure and primary functions of HIF-1 and explains the main regulatory methods of HIF-1, including the PHDs/HIF-1 /pVHL pathway, factor-inhibiting HIF (FIH), regulation of inflammatory cytokines, and the NF-B pathway. Furthermore, this paper discusses the mechanism of HIF-1 and its impact on inflammation, angiogenesis, and cartilage destruction in greater detail. We summarize previous research findings on the mechanism of HIF-1 and propose new potential treatments for RA based on the pathogenesis of HIF-1 in RA.
类风湿关节炎（RA）是一种常见的自身免疫性疾病，涉及滑膜组织的过度生长和炎症，导致关节退变和功能受损。近年来，大量研究表明关节内的缺氧微环境与RA的发生发展密切相关。人们普遍认为，RA病理变化的主要原因是关节中缺氧诱导因子-1（HIF-1）的异常表达。本文描述并阐释了HIF-1的结构和主要功能，并解释了HIF-1的主要调控方式，包括脯氨酰羟化酶/ HIF-1 /泛素蛋白连接酶E3复合体（pVHL）途径、HIF抑制因子（FIH）、炎性细胞因子的调控以及核因子-κB（NF-κB）途径。此外，本文更详细地讨论了HIF-1的作用机制及其对炎症、血管生成和软骨破坏的影响。我们总结了以往关于HIF-1作用机制的研究结果，并基于HIF-1在RA发病机制中的作用提出了RA的新潜在治疗方法。
