Author:
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.
Abstract
AbstractAngiogenic 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.
Funder
Japan Society for the Promotion of Science
Japan Agency for Medical Research and Development
Publisher
Springer Science and Business Media LLC