Liver kinase B1 inhibits smooth muscle calcification via high mobility group box 1.
Liver kinase B1 inhibits smooth muscle calcification via high mobility group box 1.
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肝激酶 B1 通过高迁移率族盒 1 抑制平滑肌钙化。
DOI：
10.1016/j.redox.2020.101828
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发表时间：
2021-01
期刊：
影响因子：
11.4
通讯作者：
Zhang W
中科院分区：
文献类型：
--
作者：
Zhang T;Li H;Ouyang C;Cao G;Gao J;Wu J;Yang J;Yu N;Min Q;Zhang C;Zhang W
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、代谢和细胞周期调节等细胞过程中起着关键作用。此外，越来越多的证据表明LKB1具有肿瘤抑制基因的功能。然而，其在血管钙化中的作用尚未见报道。将LKB1flox/flox小鼠与SM22-CreERT2转基因小鼠杂交，成年小鼠接受他莫昔芬治疗，获得平滑肌特异性lkb1敲除（LKB1SMKO）小鼠。钙化条件下LKB1表达降低，LKB1过表达对血管钙化具有保护作用。然而，高迁移率组框1 （HMGB1）过表达部分抵消了LKB1过表达诱导的血管钙化促进。机械上，LKB1可以与HMGB1结合，促进HMGB1降解。此外，LKB1SMKO小鼠血管钙化加剧，用HMGB1抑制剂甘草酸处理可减轻血管钙化。根据我们的研究结果，LKB1可能通过抑制HMGB1的表达来抑制血管钙化。钙化条件下LKB1表达降低。LKB1过表达对血管钙化具有保护作用。LKB1与HMGB1结合促进了HMGB1的降解。LKB1可能通过抑制HMGB1表达来抑制血管钙化。
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. LKB1flox/flox mice were hybridized with SM22-CreERT2 transgenic mice and adult mice received tamoxifen to obtain smooth muscle-specific LKB1-knockout (LKB1SMKO) 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, LKB1SMKO 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. LKB1 expression was reduced under calcifying conditions. LKB1 overexpression had a protective effect on vascular calcification. Binding of LKB1 to HMGB1 promoted HMGB1 degradation. LKB1 may inhibit vascular calcification by inhibiting HMGB1 expression.
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