Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, China.
Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, China; Institute for Brain Disorders, Beijing University of Chinese Medicine, Beijing, China.
Biomed Pharmacother. 2023 Sep;165:115272. doi: 10.1016/j.biopha.2023.115272. Epub 2023 Aug 4.
Tight junctions (TJs) are crucial for intercellular connections. The abnormal expression of proteins related to TJs can result in TJ destruction, structural damage, and endothelial and epithelial cell dysfunction. These factors are associated with the occurrence and progression of several diseases. Studies have shown that blood-brain barrier (BBB) damage and dysfunction are the prominent pathological features of stroke. TJs are directly associated with the BBB integrity. In this article, we first discuss the structure and function of BBB TJ-related proteins before focusing on the crucial events that cause TJ dysfunction and BBB damage, as well as the regulatory mechanisms that affect the qualitative and quantitative expression of TJ proteins during ischemic stroke. Multiple regulatory mechanisms, including phosphorylation, matrix metalloproteinases (MMPs), and microRNAs, regulate TJ-related proteins and affect BBB permeability. Some signaling pathways and mechanisms have been demonstrated to have dual functions. Hopefully, our understanding of the regulation of BBB TJs in ischemic stroke will be applied to the development of targeted medications and therapeutic therapies.
紧密连接(TJs)对于细胞间连接至关重要。与 TJs 相关的蛋白质的异常表达会导致 TJ 破坏、结构损伤以及内皮细胞和上皮细胞功能障碍。这些因素与多种疾病的发生和发展有关。研究表明,血脑屏障(BBB)损伤和功能障碍是中风的突出病理特征。TJs 与 BBB 完整性直接相关。在本文中,我们首先讨论了 BBB TJ 相关蛋白的结构和功能,然后重点介绍了导致 TJ 功能障碍和 BBB 损伤的关键事件,以及影响缺血性中风期间 TJ 蛋白定性和定量表达的调节机制。多种调节机制,包括磷酸化、基质金属蛋白酶(MMPs)和 microRNAs,调节 TJ 相关蛋白并影响 BBB 通透性。一些信号通路和机制已被证明具有双重功能。希望我们对缺血性中风中 BBB TJs 调节的理解将应用于靶向药物和治疗疗法的开发。