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タイトル別表記
AGEを介したSmad1とSmad3のリン酸化を介した新規相互作用は糖尿病性腎症の進展を制御する
著者
小野, 広幸 徳島大学大学院医科学教育部(医学専攻)
Ochi, Arisa Tokushima University
Kohashi, Masayuki Otsuka Pharmaceutical. Co. Ltd.
キーワード
diabetic nephropathy
Smad1
Smad3
phosphorylation
collagen
資料タイプ
学位論文
抄録
Diabetic nephropathy (DN) is the major cause of end-stage renal failure and is associated with increased morbidity and mortality compared with other causes of renal diseases. We previously found that Smad1 plays a critical role in the development of DN both in vitro and in vivo. However, functional interaction between Smad1 and Smad3 signaling in DN is unclear. Here, we addressed the molecular interplay between Smad1 and Smad3 signaling under a diabetic condition by using Smad3-knockout diabetic mice. Extracellular matrix (ECM) protein overexpression and Smad1 activation were observed in the glomeruli of db/db mice but were suppressed in the glomeruli of Smad3+/−; db/db mice. Smad3 activation enhanced the phosphorylation of Smad1 C-terminal domain but decreased the phosphorylation of linker domain, thus regulating Smad1 activation in advanced glycation end product-treated mesangial cells (MCs). However, forced phosphorylation of the Smad1 linker domain did not affect Smad3 activation in MCs. Phosphorylation of the Smad1 linker domain increased in Smad3+/−; db/db mice and probucol-treated db/db mice, which was consistent with the attenuation of ECM overproduction. These results indicate that Smad3 expression and activation or probucol treatment alters Smad1 phosphorylation, thus suggesting new molecular mechanisms underlying DN development and progression.
掲載誌名
Scientific Reports
ISSN
20452322
出版者
Springer Nature
8
開始ページ
10548
発行日
2018-07-12
備考
内容要旨・審査要旨・論文本文の公開
本論文は, 著者Hiroyuki Onoの学位論文として提出され, 学位審査・授与の対象となっている。
権利情報
This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
EDB ID
出版社版DOI
出版社版URL
フルテキストファイル
言語
eng
著者版フラグ
博士論文全文を含む
文科省報告番号
甲第3216号
学位記番号
甲医第1384号
学位授与年月日
2018-09-27
学位名
博士(医学)
学位授与機関
徳島大学
部局
病院
医学系