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タイトル: | Identification of MMP1 as a novel risk factor for intracranial aneurysms in ADPKD using iPSC models. |
著者: | Ameku, Tomonaga Taura, Daisuke Sone, Masakatsu Numata, Tomohiro Nakamura, Masahiro Shiota, Fumihiko Toyoda, Taro https://orcid.org/0000-0002-2948-0525 (unconfirmed) Matsui, Satoshi Araoka, Toshikazu https://orcid.org/0000-0001-9101-9417 (unconfirmed) Yasuno, Tetsuhiko Mae, Shin-Ichi Kobayashi, Hatasu Kondo, Naoya Kitaoka, Fumiyo Amano, Naoki Arai, Sayaka Ichisaka, Tomoko Matsuura, Norio Inoue, Sumiko Yamamoto, Takuya https://orcid.org/0000-0002-0022-3947 (unconfirmed) Takahashi, Kazutoshi Asaka, Isao Yamada, Yasuhiro Ubara, Yoshifumi Muso, Eri Fukatsu, Atsushi Watanabe, Akira Sato, Yasunori Nakahata, Tatsutoshi Mori, Yasuo Koizumi, Akio Nakao, Kazuwa Yamanaka, Shinya Osafune, Kenji |
著者名の別形: | 田浦, 大輔 曽根, 正勝 中村, 正裕 塩田, 文彦 豊田, 太郎 前, 伸一 小林, 果 北岡, 文美代 天野, 直己 一阪, 朋子 井上, 純子 山本, 拓也 高橋, 和利 浅香, 勲 山田, 泰広 渡辺, 亮 中畑, 龍俊 森, 泰生 小泉, 昭夫 中尾, 一和 山中, 伸弥 長船, 健二 |
発行日: | 15-Jul-2016 |
出版者: | Springer Nature |
誌名: | Scientific reports |
巻: | 6 |
論文番号: | 30013 |
抄録: | Cardiovascular complications are the leading cause of death in autosomal dominant polycystic kidney disease (ADPKD), and intracranial aneurysm (ICA) causing subarachnoid hemorrhage is among the most serious complications. The diagnostic and therapeutic strategies for ICAs in ADPKD have not been fully established. We here generated induced pluripotent stem cells (iPSCs) from seven ADPKD patients, including four with ICAs. The vascular cells differentiated from ADPKD-iPSCs showed altered Ca[2+] entry and gene expression profiles compared with those of iPSCs from non-ADPKD subjects. We found that the expression level of a metalloenzyme gene, matrix metalloproteinase (MMP) 1, was specifically elevated in iPSC-derived endothelia from ADPKD patients with ICAs. Furthermore, we confirmed the correlation between the serum MMP1 levels and the development of ICAs in 354 ADPKD patients, indicating that high serum MMP1 levels may be a novel risk factor. These results suggest that cellular disease models with ADPKD-specific iPSCs can be used to study the disease mechanisms and to identify novel disease-related molecules or risk factors. |
著作権等: | This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
URI: | http://hdl.handle.net/2433/216251 |
DOI(出版社版): | 10.1038/srep30013 |
PubMed ID: | 27418197 |
出現コレクション: | 学術雑誌掲載論文等 |
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