L-PGDS-PGD2-DP1轴调控仅存在于脑卒中后缺血区的CD36+ MGs/MΦ的吞噬作用

IF 5.1 2区 生物学 Q2 CELL BIOLOGY Cells Pub Date : 2024-10-20 DOI:10.3390/cells13201737
Takayuki Nakagomi, Aya Narita, Hideaki Nishie, Akiko Nakano-Doi, Toshinori Sawano, Yu Fukuda, Tomohiro Matsuyama
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引用次数: 0

摘要

缺血性中风等脑损伤会导致细胞死亡。虽然细胞碎片的吞噬主要由小胶质细胞/巨噬细胞(MGs/MΦs)完成,但超出其吞噬能力的过度积累会导致废物堆积,从而延迟脑细胞再生。因此,提高受损大脑清除废物的能力至关重要。脂褐素型前列腺素 D 合成酶(L-PGDS)是前列腺素 D2(PGD2)的主要合成酶,据报道可清除废物。然而,L-PGDS-PGD2 轴发挥这种作用的机制仍未阐明。本研究利用缺血性脑卒中小鼠模型发现,L-PGDS 及其下游信号通路成分(包括 PGD2 和 PGD2 受体 DP1,但不包括 DP2)在缺血区域显著上调。免疫组化显示,L-PGDS主要表达于缺血区的脑膜,而DP1则高表达于CD36+ MGs/MΦs,这些细胞特异性地存在于缺血区。此外,PGD2 处理可促进 MGs/MΦs 转化为 CD36+ 清道夫类型,并提高 CD36+ MGs/MΦs 的吞噬活性。由于CD36+ MGs/MΦs特异性地出现在脑卒中后的缺血区域,我们的研究结果表明L-PGDS-PGD2-DP1轴通过调节CD36+ MGs/MΦs的吞噬活性在脑组织修复中发挥了重要作用。
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L-PGDS-PGD2-DP1 Axis Regulates Phagocytosis by CD36+ MGs/MΦs That Are Exclusively Present Within Ischemic Areas After Stroke.

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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来源期刊
Cells
Cells Biochemistry, Genetics and Molecular Biology-Biochemistry, Genetics and Molecular Biology (all)
CiteScore
9.90
自引率
5.00%
发文量
3472
审稿时长
16 days
期刊介绍: Cells (ISSN 2073-4409) is an international, peer-reviewed open access journal which provides an advanced forum for studies related to cell biology, molecular biology and biophysics. It publishes reviews, research articles, communications and technical notes. Our aim is to encourage scientists to publish their experimental and theoretical results in as much detail as possible. There is no restriction on the length of the papers. Full experimental and/or methodical details must be provided.
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