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作者

Huiliang Cui, Lin Xie, Hanlin Lu, Cheng Cheng, Fei Xue, Zhenguo Wu, Li Liu, Lei Qiao, Cheng Zhang, Wencheng Zhang, Jianmin Yang

作者单位

Key Laboratory of Cardiovascular Remodeling and Function Research of MOE, NHC, CAMS and Shandong Province Department of Cardiology, Qilu Hospital of Shandong University, Jinan, China. yangjianminsdu@16 Department of Cardiology, Qilu Hospital of Shandong University, Jinan, China. ² Department of Cardiology, Shengjing Hospital of China Medical University, Shenyang, Liaoning Province, China. ³ Cardiovascular Disease Research Center of Shandong First Medical University, Central Hospital Affiliated to Shandong First Medical University, Jinan, China. ⁴ State Key Laboratory for Innovation and Transformation of Luobing Theory Department of Cardiology, Qilu Hospital of Shandong University, Jinan, China. zhangwencheng@sdu.edu.cn. ⁵ State Key Laboratory for Innovation and Transformation of Luobing Theory Affiliations ¹ State Key Laboratory for Innovation and Transformation of Luobing Theory com.

刊名

Cell death and differentiation

年份

2025

ISSN

1476-5403

摘要

Inflammation plays a crucial role in the progression of atherosclerosis. Junctional adhesion molecule-like protein , a type-I transmembrane glycoprotein, activates downstream signaling pathways. However, the precise role of macrophage-derived JAML in inflammation and atherosclerosis remains unclear. This study aimed to generate mice with macrophage-specific deletion or overexpression of JAML, with the focus of assessing its impact on macrophage function and elucidating its regulatory mechanism i...更多

Inflammation plays a crucial role in the progression of atherosclerosis. Junctional adhesion molecule-like protein , a type-I transmembrane glycoprotein, activates downstream signaling pathways. However, the precise role of macrophage-derived JAML in inflammation and atherosclerosis remains unclear. This study aimed to generate mice with macrophage-specific deletion or overexpression of JAML, with the focus of assessing its impact on macrophage function and elucidating its regulatory mechanism in atherosclerosis. High-throughput data screening was employed to investigate JAML expression in atherosclerosis, and macrophage-specific JAML-knockout and transgenic mice models were utilized to examine the effects of JAML on atherosclerosis. Furthermore, the role of JAML was assessed using Oil Red O staining, RNA-sequencing analysis, and co-immunoprecipitation techniques. Increased JAML expression was observed in macrophages from both mice and patients with atherosclerosis. Macrophage-specific JAML deletion attenuated atherosclerosis and inflammation, whereas macrophage-specific JAML overexpression exacerbated these conditions. Mechanistically, JAML deletion inhibited inflammation by decreasing nuclear translocation of pyruvate kinase M2 and PKM2/p65 complex formation, which consequently suppressed the nuclear factor kappa B pathway and NLRP3 inflammasome activation. Taken together, these findings demonstrate that macrophage-expressed JAML facilitates the progression of atherosclerosis by activating the NF-κB pathway and NLRP3 inflammasome through nuclear migration and phosphorylation of PKM2. Notably, our study revealed a novel mechanism for the regulation of NLRP3 inflammasome activation in atherosclerosis. Therefore, targeting JAML may be an effective treatment strategy for atherosclerosis, a condition characterized by chronic inflammation.收起

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