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Title: Identification of MMP1 as a novel risk factor for intracranial aneurysms in ADPKD using iPSC models.
Authors: Ameku, Tomonaga
Taura, Daisuke  kyouindb  KAKEN_id
Sone, Masakatsu  kyouindb  KAKEN_id
Numata, Tomohiro
Nakamura, Masahiro
Shiota, Fumihiko
Toyoda, Taro  kyouindb  KAKEN_id
Matsui, Satoshi
Araoka, Toshikazu
Yasuno, Tetsuhiko
Mae, Shin-Ichi  kyouindb  KAKEN_id
Kobayashi, Hatasu
Kondo, Naoya  kyouindb  KAKEN_id
Kitaoka, Fumiyo
Amano, Naoki
Arai, Sayaka
Ichisaka, Tomoko
Matsuura, Norio
Inoue, Sumiko
Yamamoto, Takuya  kyouindb  KAKEN_id
Takahashi, Kazutoshi
Asaka, Isao  kyouindb  KAKEN_id
Yamada, Yasuhiro
Ubara, Yoshifumi
Muso, Eri
Fukatsu, Atsushi
Watanabe, Akira
Sato, Yasunori
Nakahata, Tatsutoshi
Mori, Yasuo  kyouindb  KAKEN_id
Koizumi, Akio  kyouindb  KAKEN_id
Nakao, Kazuwa
Yamanaka, Shinya
Osafune, Kenji
Author's alias: 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
Issue Date: 15-Jul-2016
Publisher: Springer Nature
Journal title: Scientific reports
Volume: 6
Thesis number: 30013
Abstract: 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.
Rights: 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(Published Version): 10.1038/srep30013
PubMed ID: 27418197
Appears in Collections:Journal Articles

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