1. Macrophage Transcriptional Profile Identifies Lipid Catabolic Pathways That Can Be Therapeutically Targeted after Spinal Cord Injury
- Author
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Do-Hun Lee, Kara L. Spiller, Cynthia Soderblom, Vance Lemmon, Yunjiao Zhu, Kirill A. Lyapichev, John R. Bethea, Y. Zhang, J. Zha, Nicole M. Ferraro, Jae K. Lee, Stephanie L. Yahn, and Dario Motti
- Subjects
CD36 Antigens ,Male ,Ribosomal Proteins ,0301 basic medicine ,CD36 ,Mice, Transgenic ,Biology ,Mice ,03 medical and health sciences ,0302 clinical medicine ,Cell Movement ,medicine ,Animals ,Macrophage ,Spinal cord injury ,Research Articles ,Spinal Cord Injuries ,Neuroinflammation ,Bone Marrow Transplantation ,Regulation of gene expression ,Macrophages ,General Neuroscience ,Lipid metabolism ,Lipid Metabolism ,medicine.disease ,Cell biology ,Mice, Inbred C57BL ,Disease Models, Animal ,Hemagglutinins ,030104 developmental biology ,Gene Expression Regulation ,Nuclear receptor ,RNA, Ribosomal ,Immunology ,biology.protein ,Cytokines ,Leukocyte Common Antigens ,Female ,Signal transduction ,Locomotion ,030217 neurology & neurosurgery ,Signal Transduction - Abstract
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.SIGNIFICANCE STATEMENTThe 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.
- Published
- 2017
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