Macrophage Transcriptional Profile Identifies Lipid Catabolic Pathways That Can Be Therapeutically Targeted after Spinal Cord Injury

The Journal of Neuroscience, 2017 · DOI: 10.1523/JNEUROSCI.2751-16.2017 · Published: March 1, 2017

Simple Explanation

This study investigates the molecular mechanisms that regulate macrophage function after spinal cord injury (SCI). Macrophage-specific mRNA was obtained directly from the injured spinal cord and RNA sequencing was performed to investigate their transcriptional profile. The data show that at 7 days 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.

Study Duration

Not specified

Participants

Mice

Evidence Level

Not specified

Key Findings

1
Macrophages acutely after SCI (3 d) are enriched in genes associated with cell migration and cytokine signaling.
2
At a later time point (7 d), the gene expression profile transitions to reflect lipid catabolism as their primary function through the LXR/RXR and PPAR/RXR canonical pathways, including CD36.
3
Genetic deletion of CD36 is protective, resulting in improved histopathology and locomotion after SCI in CD36 KO mice.

Research Summary

This study used the RiboTag method to obtain the first macrophage-specific transcriptional profile after SCI. Data indicate that macrophages acutely after SCI (3 d) are enriched in genes associated with cell migration and cytokine signaling, transitioning to lipid catabolism at 7 d. Genetic deletion of CD36 resulted in improved outcomes, suggesting CD36 may be a potential lipid uptake mechanism that can be therapeutically targeted to improve function after SCI.

Practical Implications

Therapeutic Target Identification

CD36 and lipid catabolic pathways are identified as potential therapeutic targets for SCI.

Understanding Macrophage Function

Provides insights into the temporal changes in macrophage function after SCI, highlighting the transition from cell migration to lipid catabolism.

Application to Atherosclerosis

Druggable targets identified in atherosclerosis and other lipid-related disorders may be applicable to SCI.

Study Limitations

1
Potential contamination from other cell types despite using RiboTag method.
2
LysM-Cre mouse line labels multiple myeloid cell types, including monocytes, tissue macrophages, dendritic cells, and neutrophils.
3
Macrophages profiled represent an average of gene expression from different polarization states.

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