Department of Endocrinology, General Hospital of Central Theater Command, Wuluo Road 627, Wuhan 430070, Hubei Province, China.
The First School of Clinical Medicine, Southern Medical University, No. 1023, South Shatai Road, Baiyun District, Guangzhou, Guangdong 510515, China.
Sci Adv. 2021 May 21;7(21). doi: 10.1126/sciadv.abe6903. Print 2021 May.
Whether bone marrow modulates systemic metabolism remains unknown. Here, we found that (i) myeloid cell-specific myeloid-derived growth factor (MYDGF) deficiency exacerbated vascular inflammation, adhesion responses, endothelial injury, and atherosclerosis in vivo. (ii) Myeloid cell-specific MYDGF restoration attenuated vascular inflammation, adhesion responses and leukocyte homing and alleviated endothelial injury and atherosclerosis in vivo. (iii) MYDGF attenuated endothelial inflammation, apoptosis, permeability, and adhesion responses induced by palmitic acid in vitro. (iv) MYDGF alleviated endothelial injury and atherosclerosis through mitogen-activated protein kinase kinase kinase kinase 4 (MAP4K4)/nuclear factor κB (NF-κB) signaling. Therefore, we concluded that MYDGF inhibits endothelial inflammation and adhesion responses, blunts leukocyte homing, protects against endothelial injury and atherosclerosis in a manner involving MAP4K4/NF-κB signaling, and serves as a cross-talk factor between bone marrow and arteries to regulate the pathophysiology of arteries. Bone marrow functions as an endocrine organ and serves as a potential therapeutic target for metabolic disorders.
骨髓是否调节全身代谢尚不清楚。在这里，我们发现：（i）髓系细胞特异性髓系衍生生长因子（MYDGF）缺乏会加剧体内血管炎症、黏附反应、内皮损伤和动脉粥样硬化。（ii）髓系细胞特异性 MYDGF 恢复会减弱体内的血管炎症、黏附反应和白细胞归巢，并减轻内皮损伤和动脉粥样硬化。（iii）MYDGF 可减轻体外棕榈酸诱导的内皮炎症、细胞凋亡、通透性和黏附反应。（iv）MYDGF 通过丝裂原活化蛋白激酶激酶激酶激酶 4（MAP4K4）/核因子 κB（NF-κB）信号通路减轻内皮损伤和动脉粥样硬化。因此，我们得出结论，MYDGF 通过 MAP4K4/NF-κB 信号通路抑制内皮炎症和黏附反应，抑制白细胞归巢，保护内皮免受损伤和动脉粥样硬化，充当骨髓和动脉之间的交流因子，调节动脉的病理生理学。骨髓是内分泌器官，是代谢紊乱的潜在治疗靶点。
