Macrophage transcriptional profile identifies lipid catabolic pathways that can be therapeutically targeted after spinal cord injury
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE84737 | GEO | 2017/01/28
SECONDARY ACCESSION(S): PRJNA330973
REPOSITORIES: GEO
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Project description:OL translatome was determined in female RiboTag:Plp1-CreERT2 mice (C57Bl6 background) at 2, 10, and, 42 days after moderate contusive T9 SCI. Ribotag expression was induced by daily tamoxifen injections (1 mg i.p. over 8 days). Three weeks after completion of the induction protocol moderate contusive SCI was performed at T9 level (IH imactor, 50 kdyn). Uninjured mice (naive) were used as controls. At the time of surgery, animal age was 10-12 weeks. After euthanasia, RNA was isolated from a 5 mm spinal cord segment spanning the injury epicenter. OL tranlsatome was immunopurified using anti-HA antibody and protein A/G coupled magnetic beads following the Ribotag protocol. Total spinal cord RNA and OL translatome RNA samples were analyzed by RNASeq. Each biological sample was prepared by pooling material from two mice (3 biological samples representing 6 animals were used for each timepoint).
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Project description:After spinal cord injury (SCI), infiltrating macrophages undergo excessive phagocytosis of myelin and cellular debris, forming lipid-laden foamy macrophages. To understand their role in the cellular pathology of SCI, investigation of foamy macrophage phenotype in vitro revealed a unique inflammatory profile, increased reactive oxygen species (ROS) production, and mitochondrialdysfunction. Bioinformatic analysis identified PI3K as a regulator of inflammation in foamy macrophages, and pharmacological inhibition of this pathway decreased lipid content and inflammatory cytokine and ROS production in these cells. Macrophage-specific inhibition of PI3K using liposomes significantly decreased foamy macrophages at the injury site after a mid-thoracic contusive SCI in mice. RNA sequencing and in vitro analysis of foamy macrophages revealed increased autophagy after PI3K inhibition as a potential mechanism for reduced cellular lipid accumulation. Together, our data suggest that formation of pro-inflammatory foamy macrophages after SCI is due to activation of PI3K signaling that leads to decreased autophagy.
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Project description:LncRNAs played a crucial role in the cell growth, development and some diseases relating to central nerve system.This study suggest that with regulating the LncRNAs expression level we might design novel therapy for spinalcord injury. In this dataset, we profiled the expression pattern of LncRNAs by microarray method after spinal cord injury (SCI). Through Gene ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis seek LncRNAs potential function in the repair of spinal cord injury. Fifteen samples were analyzed. In these sample, we divided into five groups (sham operation, 1 day post-injured, 3 days post-injured, 1 week post-injued and 3 weeks post-injured) and each group contained three mice.After RNA extraction,RNA form mice in the same group were mixed by equal mass for the preparation of microarray.Compared with spinal cord without injury, the differential expression level of LncRNAs had a few changes at 1day post-injury, reached the peak at 1 week after SCI, and subsequently declined until 3 weeks post-injury. Genes with an FDR≤0.05 and a fold-change ≥2 were selected. Subsequently we analysis the significant differential expression genes.
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