Scientific reports · 2016
Identification of MMP1 as a novel risk factor for intracranial aneurysms in ADPKD using iPSC models.
СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Ameku Tomonaga, Taura Daisuke, Sone Masakatsu, Numata Tomohiro, Nakamura Masahiro, Shiota Fumihiko, Toyoda Taro, Matsui Satoshi, Araoka Toshikazu, Yasuno Tetsuhiko, Mae Shin-Ichi, Kobayashi Hatasu, Kondo Naoya, Kitaoka Fumiyo, Amano Naoki, Arai Sayaka, Ichisaka Tomoko, Matsuura Norio, Inoue Sumiko, Yamamoto Takuya, 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
Аннотация
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.