Liver kinase B1 inhibits smooth muscle calcification via high mobility group box 1
Tianran Zhang,
Hongxuan Li,
Changhan Ouyang,
Guangqing Cao,
Jiangang Gao,
Jiliang Wu,
Jianmin Yang,
Nengwang Yu,
Qing Min,
Cheng Zhang,
Wencheng Zhang
Affiliations
Tianran Zhang
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
Hongxuan Li
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
Changhan Ouyang
School of Pharmacy, Hubei University of Science and Technology, Xianning, Hubei, China
Guangqing Cao
Department of Cardiovascular Surgery, Qilu Hospital of Shandong University, Jinan, Shandong, China
Jiangang Gao
School of Life Science and Key Laboratory of the Ministry of Education for Experimental Teratology, Shandong University, Jinan, China
Jiliang Wu
School of Pharmacy, Hubei University of Science and Technology, Xianning, Hubei, China
Jianmin Yang
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
Nengwang Yu
Department of Urology, Qilu Hospital of Shandong University, Jinan, China
Qing Min
School of Pharmacy, Hubei University of Science and Technology, Xianning, Hubei, China; Corresponding author. No. 88, Xianning Rd, Xianning, Hubei, 437100, China.
Cheng Zhang
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; Corresponding author. No. 107, Wen Hua Xi Rd, Jinan, Shandong, 250012, China.
Wencheng Zhang
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; Corresponding author. No. 107, Wen Hua Xi Rd, Jinan, Shandong, 250012, China.
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.
