Macrophage transcriptional profile identifies lipid catabolic pathways that can be therapeutically targeted after spinal cord injury

Y. Zhu, K. Lyapichev, D. H. Lee, D. Motti, N. M. Ferraro, Y. Zhang, S. Yahn, C. Soderblom, J. Zha, John R Bethea, K. L. Spiller, V. P. Lemmon, Jae K. Lee

Research output: Contribution to journalArticle

19 Scopus citations

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 macrophagespecific transcriptional profile after SCI and highlight the lipid catabolic pathway as an important macrophage function that can be therapeutically targeted after SCI.

Original languageEnglish (US)
Pages (from-to)2362-2376
Number of pages15
JournalJournal of Neuroscience
Volume37
Issue number9
DOIs
StatePublished - Mar 1 2017

Keywords

  • Axon regeneration
  • Fibrotic scar
  • Foamy macrophages
  • Glial scar
  • Myelin laden macrophages
  • Neuroinflammation

ASJC Scopus subject areas

  • Neuroscience(all)

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    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. (2017). Macrophage transcriptional profile identifies lipid catabolic pathways that can be therapeutically targeted after spinal cord injury. Journal of Neuroscience, 37(9), 2362-2376. https://doi.org/10.1523/JNEUROSCI.2751-16.2017