巨噬细胞转录谱鉴定出脊髓损伤后可作为治疗靶点的脂质分解代谢途径。
Macrophage Transcriptional Profile Identifies Lipid Catabolic Pathways That Can Be Therapeutically Targeted after Spinal Cord Injury.
作者信息
Zhu Y, Lyapichev K, Lee D H, Motti D, Ferraro N M, Zhang Y, Yahn S, Soderblom C, Zha J, Bethea J R, Spiller K L, Lemmon V P, Lee J K
机构信息
Miami Project to Cure Paralysis, Department of Neurological Surgery, School of Medicine and.
School of Biomedical Engineering, Science and Health Systems, Drexel University, Philadelphia, Pennsylvania 19104.
出版信息
J Neurosci. 2017 Mar 1;37(9):2362-2376. doi: 10.1523/JNEUROSCI.2751-16.2017. Epub 2017 Jan 27.
Although infiltrating macrophages influence many pathological processes after spinal cord injury (SCI), the intrinsic molecular mechanisms that regulate their function are poorly understood. A major hurdle has been dissecting macrophage-specific functions from those in other cell types as well as understanding how their functions change over time. Therefore, we used the RiboTag method to obtain macrophage-specific mRNA directly from the injured spinal cord in mice and performed RNA sequencing to investigate their transcriptional profile. Our data show that at 7 d after SCI, macrophages are best described as foam cells, with lipid catabolism representing the main biological process, and canonical nuclear receptor pathways as their potential mediators. Genetic deletion of a lipoprotein receptor, CD36, reduces macrophage lipid content and improves lesion size and locomotor recovery. Therefore, we report the first macrophage-specific transcriptional profile after SCI and highlight the lipid catabolic pathway as an important macrophage function that can be therapeutically targeted after SCI. The intrinsic molecular mechanisms that regulate macrophage function after spinal cord injury (SCI) are poorly understood. We obtained macrophage-specific mRNA directly from the injured spinal cord and performed RNA sequencing to investigate their transcriptional profile. Our data show that at 7 d after SCI, macrophages are best described as foam cells, with lipid catabolism representing the main biological process and canonical nuclear receptor pathways as their potential mediators. Genetic deletion of a lipoprotein receptor, CD36, reduces macrophage lipid content and improves lesion size and locomotor recovery. Therefore, we report the first macrophage-specific transcriptional profile after SCI and highlight the lipid catabolic pathway as an important macrophage function that can be therapeutically targeted after SCI.
尽管浸润的巨噬细胞会影响脊髓损伤（SCI）后的许多病理过程，但其调节功能的内在分子机制却知之甚少。一个主要障碍是将巨噬细胞的特定功能与其他细胞类型的功能区分开来，以及了解它们的功能如何随时间变化。因此，我们使用RiboTag方法直接从小鼠受伤的脊髓中获取巨噬细胞特异性mRNA，并进行RNA测序以研究其转录谱。我们的数据表明，在脊髓损伤后7天，巨噬细胞最好被描述为泡沫细胞，脂质分解代谢是主要的生物学过程，经典核受体途径是其潜在的介导因子。脂蛋白受体CD36的基因缺失可降低巨噬细胞脂质含量，并改善损伤大小和运动功能恢复。因此，我们报告了脊髓损伤后首个巨噬细胞特异性转录谱，并强调脂质分解代谢途径是脊髓损伤后可作为治疗靶点的重要巨噬细胞功能。脊髓损伤（SCI）后调节巨噬细胞功能的内在分子机制尚不清楚。我们直接从受伤的脊髓中获取巨噬细胞特异性mRNA，并进行RNA测序以研究其转录谱。我们的数据表明，在脊髓损伤后7天，巨噬细胞最好被描述为泡沫细胞，脂质分解代谢是主要的生物学过程，经典核受体途径是其潜在的介导因子。脂蛋白受体CD36的基因缺失可降低巨噬细胞脂质含量，并改善损伤大小和运动功能恢复。因此，我们报告了脊髓损伤后首个巨噬细胞特异性转录谱，并强调脂质分解代谢途径是脊髓损伤后可作为治疗靶点的重要巨噬细胞功能。
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