Identification of MMP1 As a Novel Risk Factor for Intracranial Aneurysms in ADPKD Using IPSC Models

Overview

Journal Sci Rep

Specialty Science

Date 2016 Jul 16

PMID 27418197

Citations 20

Authors

Tomonaga Ameku

Daisuke Taura

Masakatsu Sone

Tomohiro Numata

Masahiro Nakamura

Fumihiko Shiota

Taro Toyoda

Satoshi Matsui

Toshikazu Araoka

Tetsuhiko Yasuno

Shin-Ichi Mae

Hatasu Kobayashi

Naoya Kondo

Fumiyo Kitaoka

Naoki Amano

Sayaka Arai

Tomoko Ichisaka

Norio Matsuura

Sumiko Inoue

Takuya Yamamoto

Kazutoshi Takahashi

Isao Asaka

Yasuhiro Yamada

Yoshifumi Ubara

Eri Muso

Atsushi Fukatsu

Akira Watanabe

Yasunori Sato

Tatsutoshi Nakahata

Yasuo Mori

Akio Koizumi

Kazuwa Nakao

Shinya Yamanaka

Kenji Osafune

Affiliations

Soon will be listed here.

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.

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