Angiogenic and inflammatory responses in human induced microglia-like (iMG) cells from patients with Moyamoya disease

Angiogenic factors associated with Moyamoya disease (MMD) are overexpressed in M2 polarized microglia in ischemic stroke, suggesting that microglia may be involved in the pathophysiology of MMD; however, existing approaches are not applicable to explore this hypothesis. Herein we applied blood induc...

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Published in:Scientific reports 2023-09, Vol.13 (1), p.14842-14842, Article 14842
Main Authors: Shirozu, Noritoshi, Ohgidani, Masahiro, Hata, Nobuhiro, Tanaka, Shunya, Inamine, Shogo, Sagata, Noriaki, Kimura, Tetsuaki, Inoue, Ituro, Arimura, Koichi, Nakamizo, Akira, Nishimura, Ataru, Maehara, Naoki, Takagishi, Soh, Iwaki, Katsuma, Nakao, Tomohiro, Masuda, Keiji, Sakai, Yasunari, Mizoguchi, Masahiro, Yoshimoto, Koji, Kato, Takahiro A.
Format: Article
Language:English
Subjects:
631/378/2596/1953
631/378/2607
Angiogenesis
Biological activity
Carotid arteries
Cerebrovascular diseases
Cytokines
Disease
Gelatinase B
Gene expression
Humanities and Social Sciences
Hypotheses
Inflammation
Informed consent
Ischemia
Microglia
Monocytes
Moyamoya disease
multidisciplinary
Mutation
Neurosurgery
Pathogenesis
Science
Science (multidisciplinary)
Stroke
Transforming growth factor-b1
Vascular diseases
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Summary:Angiogenic factors associated with Moyamoya disease (MMD) are overexpressed in M2 polarized microglia in ischemic stroke, suggesting that microglia may be involved in the pathophysiology of MMD; however, existing approaches are not applicable to explore this hypothesis. Herein we applied blood induced microglial-like (iMG) cells. We recruited 25 adult patients with MMD and 24 healthy volunteers. Patients with MMD were subdivided into progressive (N = 7) or stable (N = 18) group whether novel symptoms or radiographic advancement of Suzuki stage within 1 year was observed or not. We produced 3 types of iMG cells; resting, M1-, and M2-induced cells from monocytes, then RNA sequencing followed by GO and KEGG pathway enrichment analysis and qPCR assay were performed. RNA sequencing of M2-induced iMG cells revealed that 600 genes were significantly upregulated (338) or downregulated (262) in patients with MMD. Inflammation and immune-related factors and angiogenesis-related factors were specifically associated with MMD in GO analysis. qPCR for MMP9 , VEGFA , and TGFB1 expression validated these findings. This study is the first to demonstrate that M2 microglia may be involved in the angiogenic process of MMD. The iMG technique provides a promising approach to explore the bioactivity of microglia in cerebrovascular diseases.
ISSN:2045-2322
2045-2322
DOI:10.1038/s41598-023-41456-z