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Macrophage Transcriptional Profile Identifies Lipid Catabolic Pathways That Can Be Therapeutically Targeted after Spinal Cord Injury
Journal article   Open access   Peer reviewed

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, J R Bethea, …
The Journal of neuroscience, v 37(9), pp 2362-2376
01 Mar 2017
DOI: https://doi.org/10.1523/JNEUROSCI.2751-16.2017
PMID: 28130359
Featured in Collection :   UN Sustainable Development Goals @ Drexel
url
https://doi.org/10.1002/14651858.cd006911.pub4View
Published, Version of Record (VoR)Open Access (License Unspecified),  Open
url
https://doi.org/10.1523/JNEUROSCI.2751-16.2017View
Published, Version of Record (VoR) Open

Abstract

Animals Bone Marrow Transplantation CD36 Antigens - genetics CD36 Antigens - metabolism Cell Movement - genetics Cytokines - genetics Cytokines - metabolism Disease Models, Animal Female Gene Expression Regulation - genetics Hemagglutinins - metabolism Leukocyte Common Antigens - genetics Leukocyte Common Antigens - metabolism Lipid Metabolism - genetics Lipid Metabolism - physiology Locomotion Macrophages - metabolism Male Mice Mice, Inbred C57BL Mice, Transgenic Ribosomal Proteins - genetics Ribosomal Proteins - metabolism RNA, Ribosomal - administration & dosage Signal Transduction - genetics Spinal Cord Injuries - pathology Spinal Cord Injuries - physiopathology Spinal Cord Injuries - surgery
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.

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91 citations in Web of Science
87 citations in Scopus

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UN Sustainable Development Goals (SDGs)

This publication has contributed to the advancement of the following goals:

#3 Good Health and Well-Being

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Collaboration types
Domestic collaboration
Web of Science research areas
Neurosciences
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