Macrophage Transcriptional Profile Identifies Lipid Catabolic Pathways That Can Be Therapeutically Targeted after Spinal Cord Injury
| Autor: | 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, Dario Motti |
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| Rok vydání: | 2017 |
| Předmět: |
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 |
| Zdroj: | The Journal of Neuroscience. 37:2362-2376 |
| ISSN: | 1529-2401 0270-6474 |
| DOI: | 10.1523/jneurosci.2751-16.2017 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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