骨髓内皮细胞调节糖尿病中的骨髓形成
Friedrich Felix Hoyer1, Xinyi Zhang2,3, Emilie Coppin2
1Center for Systems Biology and Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Simches Research Building, Boston (F.F.H., M.J.S., D.R., C.S.A., Y.I., K.N., F.K.S., M.N.).
Circulation
|April 23, 2020
概括
糖尿病通过降低干细胞安静的因素Cxcl12来破坏骨髓造血. 内皮细胞的EGFR信号通常会抑制干细胞的增殖,但是干细胞的干扰会导致糖尿病的并发症,如伤口愈合的延迟和动脉样硬化.
科学领域:
- 血液学
- 内分泌学
- 血管生物学
背景情况:
- 糖尿病影响了美国人口的很大一部分,导致严重的血管并发症.
- 骨髓造血在糖尿病并发症中的作用尚未完全理解.
- 这项研究调查了骨髓内皮细胞如何影响糖尿病炎症性髓细胞的产生.
研究的目的:
- 阐明骨髓内皮细胞在与糖尿病相关的血液形成中的作用.
- 鉴定糖尿病对造血干细胞和原生细胞 (HSPC) 生产的失调机制.
- 探索内皮生长因子受体 (Egfr) 在骨髓形成中的信号传递的功能.
主要方法:
- 在三种糖尿病小鼠模型中测试的白细胞和HSPCs (链杆菌素,高脂肪饮食,db/db).
- 使用流细胞计和表达特征分析骨髓内皮细胞.
- 产生了内皮特异性Egfr删除 (Cdh5-Egfr) 的小鼠,以研究其功能作用.
主要成果:
- 糖尿病增加了HSPC的增殖和循环的骨髓细胞.
- 糖尿病小鼠表现出干细胞保留因子内皮Cxcl12的减少.
- 内皮EGFR信号干扰导致HSPC扩散和骨髓产生的增加,加剧了伤口愈合缺陷和动脉样硬化.
结论:
- 骨髓内皮细胞是糖尿病引起的血液形成失调的关键因素.
- 糖尿病会损害内皮Cxcl12的产生,促进干细胞的增殖.
- 在糖尿病中,内皮EGFR信号传递是控制HSPC增殖和骨髓细胞生成的关键反调节途径.
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