血小板衍生生增长因子在细胞内发出信号,促进下丘脑炎症和肥胖
Akira Okekawa1, Tsutomu Wada2, Yasuhiro Onogi1,3
1Department of Clinical Pharmacology, University of Toyama, 2630 Sugitani, Toyama, 930-0194, Japan.
Molecular medicine (Cambridge, Mass.)
|February 5, 2024
概括
血小板衍生生长因子 (PDGF) 受体信号传递在下丘脑内皮质细胞中驱动肥胖症的进展. 阻止这种途径可以减少炎症和体重增加,从而成为潜在的治疗点.
科学领域:
- 神经科学是一个神经科学.
- 代谢过程中的代谢.
- 免疫学 免疫学 免疫学
背景情况:
- 细胞对于血脑屏障的完整性至关重要,可能会影响炎症.
- 皮质细胞在下丘脑慢性炎症和与肥胖相关的能量代谢中的作用仍然在很大程度上是未知的.
- 血小板衍生生长因子 (PDGF) 信号调节细胞周围细胞功能,并在本研究中进行了研究.
研究的目的:
- 为了研究皮质细胞,特别是PDGF受体β信号传递对下丘脑炎症和肥胖的能量代谢的影响.
- 阐明皮细胞对肥胖病理生理学的贡献机制.
主要方法:
- 利用他莫西芬诱导的全身和神经元特异性PDGF受体β淘汰赛小鼠,食高脂肪饮食.
- 评估了用脂多糖和PDGF-BB刺激的人类大脑细胞 (HBPCs) 的细胞内能量代谢和信号传递.
- 分析了细胞周围细胞的分泌物及其对巨细胞两极分化的影响.
主要成果:
- 在高脂肪饮食下,小鼠PDGF受体β的系统性淘汰会减少体重增加和下丘脑炎症标志物.
- 刺激PDGF-BB诱导HBPCs中的一种促炎性分泌物,促进巨细胞的两极分化.
- 皮细胞中PDGF受体β的淘汰会降低下丘脑中的炎症性化学激素表达 (例如CXCL5).
结论:
- 在下丘脑周细胞中PDGF受体β信号传递通过秘密分子调节促进了巨细胞的极化.
- 这种由细胞周围细胞驱动的炎症过程有助于肥胖的进展.
- 向皮细胞中的PDGF受体β可能为肥胖症治疗提供一种新的策略.
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