Hunan Province Innovative Training Base for Medical Postgraduates, Clinical Anatomy & Reproductive Medicine Application Institute, University of South China, Hengyang 421001, China; Institute of Basic Medical Sciences, Guilin Medical University, Guilin 541199, Guangxi, China.
Hunan Province Innovative Training Base for Medical Postgraduates, Clinical Anatomy & Reproductive Medicine Application Institute, University of South China, Hengyang 421001, China.
Cytokine. 2020 Nov;135:155242. doi: 10.1016/j.cyto.2020.155242. Epub 2020 Aug 13.
Midkine (MK) is a low molecular-weight protein that was first identified as the product of a retinoic acid-responsive gene involved in embryonic development. Recent studies have indicated that MK levels are related to various diseases, including cardiovascular disease (CVD), renal disease and autoimmune disease. MK is a growth factor involved in multiple pathophysiological processes, such as inflammation, the repair of damaged tissues and cancer. The pathophysiological roles of MK are diverse. MK enhances the recruitment and migration of inflammatory cells upon inflammation directly and also through induction of chemokines, and contributes to tissue damage. In lung endothelial cells, oxidative stress increased the expression of MK, which induced angiotensin-converting enzyme (ACE) expression and the consequent conversion from Ang I to Ang II, leading to further oxidative stress. MK inhibited cholesterol efflux from macrophages by reducing ATP-binding cassette transporter A1 (ABCA1) expression, which is involved in lipid metabolism, suggesting that MK is an important positive factor involved in inflammation, oxidative stress and lipid metabolism. Furthermore, MK can regulate the expansion, differentiation and activation of T cells as well as B-cell survival; mediate angiogenic and antibacterial activity; and possess anti-apoptotic activity. In this paper, we summarize the pathophysiological roles of MK in human disease.
中期因子（MK）是一种低分子量蛋白，最初被鉴定为参与胚胎发育的视黄酸反应基因的产物。最近的研究表明，MK 水平与各种疾病有关，包括心血管疾病（CVD）、肾脏疾病和自身免疫性疾病。MK 是一种参与多种病理生理过程的生长因子，如炎症、受损组织修复和癌症。MK 的病理生理作用多种多样。MK 通过诱导趋化因子直接促进炎症时炎症细胞的募集和迁移，并有助于组织损伤。在肺内皮细胞中，氧化应激增加了 MK 的表达，这诱导了血管紧张素转换酶（ACE）的表达，从而导致 Ang I 转化为 Ang II，进一步导致氧化应激。MK 通过降低参与脂质代谢的三磷酸腺苷结合盒转运体 A1（ABCA1）的表达，抑制巨噬细胞中的胆固醇流出，表明 MK 是参与炎症、氧化应激和脂质代谢的重要正因子。此外，MK 可以调节 T 细胞的扩增、分化和激活以及 B 细胞的存活；介导血管生成和抗菌活性；并具有抗细胞凋亡活性。本文总结了 MK 在人类疾病中的病理生理作用。
