L-PGDS-PGD2-DP1 Axis Regulates Phagocytosis by CD36 + MGs/MΦs That Are Exclusively Present Within Ischemic Areas After Stroke.

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  • Additional Information
    • Source:
      Publisher: MDPI Country of Publication: Switzerland NLM ID: 101600052 Publication Model: Electronic Cited Medium: Internet ISSN: 2073-4409 (Electronic) Linking ISSN: 20734409 NLM ISO Abbreviation: Cells Subsets: MEDLINE
    • Publication Information:
      Original Publication: Basel, Switzerland : MDPI
    • Subject Terms:
      Phagocytosis* ; Prostaglandin D2*/metabolism ; CD36 Antigens*/metabolism ; Macrophages*/metabolism ; Lipocalins*/metabolism ; Lipocalins*/genetics ; Stroke*/metabolism ; Stroke*/pathology ; Microglia*/metabolism ; Microglia*/pathology ; Mice, Inbred C57BL*; Animals ; Mice ; Male ; Intramolecular Oxidoreductases/metabolism ; Brain Ischemia/metabolism ; Brain Ischemia/pathology ; Signal Transduction ; Ischemic Stroke/metabolism ; Ischemic Stroke/pathology ; Disease Models, Animal
    • Abstract:
      Brain injuries, such as ischemic stroke, cause cell death. Although phagocytosis of cellular debris is mainly performed by microglia/macrophages (MGs/MΦs), excessive accumulation beyond their phagocytic capacities results in waste product buildup, delaying brain cell regeneration. Therefore, it is essential to increase the potential for waste product removal from damaged brains. Lipocalin-type prostaglandin D synthase (L-PGDS) is the primary synthase for prostaglandin D2 (PGD2) and has been reported as a scavenger of waste products. However, the mechanism by which the L-PGDS-PGD2 axis exerts such an effect remains unelucidated. In this study, using a mouse model of ischemic stroke, we found that L-PGDS and its downstream signaling pathway components, including PGD2 and PGD2 receptor DP1 (but not DP2), were significantly upregulated in ischemic areas. Immunohistochemistry revealed the predominant expression of L-PGDS in the leptomeninges of ischemic areas and high expression levels of DP1 in CD36 + MGs/MΦs that were specifically present within ischemic areas. Furthermore, PGD2 treatment promoted the conversion of MGs/MΦs into CD36 + scavenger types and increased phagocytic activities of CD36 + MGs/MΦs. Because CD36 + MGs/MΦs specifically appeared within ischemic areas after stroke, our findings suggest that the L-PGDS-PGD2-DP1 axis plays an important role in brain tissue repair by regulating phagocytic activities of CD36 + MGs/MΦs.
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    • Grant Information:
      23K06815 Japan Society for the Promotion of Science (JSPS) KAKENHI
    • Contributed Indexing:
      Keywords: CD36; ischemic stroke; lipocalin-type prostaglandin D synthase; microglia/macrophages; pericyte; phagocytosis; prostaglandin D2; scavenger
    • Accession Number:
      RXY07S6CZ2 (Prostaglandin D2)
      0 (CD36 Antigens)
      0 (Lipocalins)
      EC 5.3.99.2 (prostaglandin R2 D-isomerase)
      EC 5.3.- (Intramolecular Oxidoreductases)
    • Publication Date:
      Date Created: 20241025 Date Completed: 20241025 Latest Revision: 20250127
    • Publication Date:
      20250127
    • Accession Number:
      PMC11505914
    • Accession Number:
      10.3390/cells13201737
    • Accession Number:
      39451255