Department of Biomedical Laboratory Science, Konyang University, Daejeon 35365, Korea.
Mol Cells. 2021 Apr 30;44(4):195-206. doi: 10.14348/molcells.2021.0020.
Brain disease is known to cause irrevocable and fatal loss of biological function once damaged. One of various causes of its development is damage to neuron cells caused by hyperactivated microglia, which function as immune cells in brain. Among the genes expressed in microglia stimulated by various antigens, annexin A1 (ANXA1) is expressed in the early phase of the inflammatory response and plays an important role in controlling the immune response. In this study, we assessed whether ANXA1 can be a therapeutic target gene for the initial reduction of the immune response induced by microglia to minimize neuronal damage. To address this, mouse-origin microglial cells were stimulated to mimic an immune response by lipopolysaccharide (LPS) treatment. The LPS treatment caused activation of ANXA1 gene and expression of inflammatory cytokines. To assess the biological function in microglia by the downregulation of ANXA1 gene, cells were treated with short hairpin RNA-ANXA1. Downregulated ANXA1 affected the function of mitochondria in the microglia and showed reduced neuronal damage when compared to the control group in the co-culture system. Taken together, our results showed that ANXA1 could be used as a potential therapeutic target for inflammation-related neurodegenerative diseases.
脑疾病一旦受损，会造成不可逆转和致命的生物功能丧失。其发展的一个原因是被过度激活的小胶质细胞引起的神经元细胞损伤，小胶质细胞在大脑中充当免疫细胞。在各种抗原刺激的小胶质细胞中表达的基因中，膜联蛋白 A1（ANXA1）在炎症反应的早期阶段表达，并在控制免疫反应中发挥重要作用。在这项研究中，我们评估了 ANXA1 是否可以作为治疗靶点基因，以减少小胶质细胞诱导的免疫反应的初始阶段，从而最大限度地减少神经元损伤。为了解决这个问题，用脂多糖（LPS）处理模拟免疫反应来刺激鼠源性小胶质细胞。LPS 处理导致 ANXA1 基因的激活和炎症细胞因子的表达。通过下调 ANXA1 基因来评估小胶质细胞中的生物学功能，用短发夹 RNA-ANXA1 处理细胞。与对照组相比，下调的 ANXA1 影响了小胶质细胞中线粒体的功能，在共培养系统中显示出减少的神经元损伤。总之，我们的研究结果表明，ANXA1 可用作与炎症相关的神经退行性疾病的潜在治疗靶点。
