The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese National Health Commission and Chinese Academy of Medical Sciences, The State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Department of Cardiology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China.
School of Pharmacy, Hubei University of Science and Technology, Xianning, Hubei, China.
Redox Biol. 2021 Jan;38:101828. doi: 10.1016/j.redox.2020.101828. Epub 2020 Dec 6.
Vascular calcification is a common pathological feature of atherosclerosis, chronic kidney disease, vascular injury, and aging. Liver kinase B1 (LKB1) plays pivotal roles in cellular processes such as apoptosis, metabolism, and cell cycle regulation. In addition, growing evidence has indicated that LKB1 functions as a tumor suppressor gene. However, its role in vascular calcification has not been reported. LKB1 mice were hybridized with SM22-CreER transgenic mice and adult mice received tamoxifen to obtain smooth muscle-specific LKB1-knockout (LKB1) mice. LKB1 expression was decreased under calcifying conditions, and LKB1 overexpression had a protective effect on vascular calcification. However, high mobility group box 1 (HMGB1) overexpression partially counteracted the promotion of vascular calcification induced by LKB1 overexpression. Mechanically, LKB1 could bind to HMGB1 to promote HMGB1 degradation. Furthermore, LKB1 mice showed intensified vascular calcification, which was alleviated by treatment with the HMGB1 inhibitor glycyrrhizic acid. Based on our results, LKB1 may inhibit vascular calcification via inhibiting HMGB1 expression.
血管钙化是动脉粥样硬化、慢性肾病、血管损伤和衰老的常见病理特征。肝激酶 B1（LKB1）在细胞凋亡、代谢和细胞周期调控等细胞过程中发挥着关键作用。此外，越来越多的证据表明 LKB1 作为一种肿瘤抑制基因发挥作用。然而，其在血管钙化中的作用尚未被报道。将 LKB1 敲除（LKB1）小鼠与 SM22-CreER 转基因小鼠杂交，成年小鼠接受他莫昔芬处理，获得平滑肌特异性 LKB1 敲除（LKB1）小鼠。在钙化条件下，LKB1 的表达减少，而过表达 LKB1 对血管钙化有保护作用。然而，高迁移率族蛋白 B1（HMGB1）的过表达部分抵消了 LKB1 过表达诱导的血管钙化的促进作用。在机制上，LKB1 可以与 HMGB1 结合，促进 HMGB1 的降解。此外，LKB1 小鼠表现出更严重的血管钙化，用 HMGB1 抑制剂甘草酸处理后可减轻血管钙化。基于我们的结果，LKB1 可能通过抑制 HMGB1 的表达来抑制血管钙化。
