Mechanisms of moyamoya-susceptible gene expression by interferon and the establishment of preventive medicine for cerebrovascular disease

2016 Fiscal Year Final Research Report

• Project/Area Number: 26460801
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Hygiene and public health
• Research Institution: St. Marianna University School of Medicine (2015-2016); Kyoto University (2014)
• Principal Investigator: Hitomi Toshiaki 聖マリアンナ医科大学, 医学部, 准教授 (90405275)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: 予防医学 / もやもや病 / mysterin（RNF213） / インターフェロン / 脳血管疾患 / 血管内皮細胞 / iPS細胞 / 感染症

Outline of Final Research Achievements

Mysterin (RNF213) is a susceptibility gene for moyamoya disease (MMD) and its coding variant, p.R4810K, is a common founder variant in East Asian countries. Several angiogenic and anti-angiogenic factors [including interferons (IFNs), IFN-β and IFN-γ] induced transcriptional expression of mysterin in human umbilical vein endothelial cells (HUVECs). In HUVECs, upregulation of mysterin by IFN-β is mediated by a STAT1-binding site on the mysterin gene promoter. The anti-angiogenic activities of IFN-β are partially rescued by siRNA for STAT1, and completely rescued by siRNA for mysterin. Treatment with IFN-β induced mysterin mRNA and decreased angiogenesis in induced pluripotent stem cells-derived vascular endothelial cells (iPSECs) derived from control subjects and patients with MMD. Our data suggest that mysterin mediates the IFN-β anti-angiogenic signaling pathway; MMD may impair angiogenesis in patients with infectious or autoimmune disease.

Free Research Field

医歯薬学