Novel Interplay Between Smad1 and Smad3 Phosphorylation via AGE Regulates the Progression of Diabetic Nephropathy

• Material Type: 博士論文
• Title: Novel Interplay Between Smad1 and Smad3 Phosphorylation via AGE Regulates the Progression of Diabetic Nephropathy
• Author/Editor: Ono, Hiroyuki; Abe, Hideharu; Sakurai, Akiko; Ochi, Arisa; Tominaga, Tatsuya; Tamaki, Masanori; Kishi, Seiji; Murakami, Taichi; Nagai, Kojiro; Kohashi, Masayuki; Doi, Toshio
• Author Heading: Ono, Hiroyuki; Abe, Hideharu; Sakurai, Akiko; Ochi, Arisa; Tominaga, Tatsuya; Tamaki, Masanori; Kishi, Seiji; Murakami, Taichi; Nagai, Kojiro; Kohashi, Masayuki; Doi, Toshio
• Publication, Distribution, etc.: Springer Nature
• Publication Date: 2018-07-12
• Publication Date (W3CDTF): 2018-07-12
• Alternative Title: 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
• Periodical title: Scientific Reports
• No. or year of volume/issue: 8
• Volume: 8
• Pages: 10548-
• ISSN (Periodical Title): ISSN : 2045-2322
• Degree grantor/type: 徳島大学
• Date Granted: 2018-09-27
• Dissertation Number: 甲第3216号
• Degree Type: 博士（医学）
• Text Language Code: eng
• Subject Heading: diabetic nephropathy; Smad1; Smad3; phosphorylation; collagen
• Target Audience: 一般
• Note (General): 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.
• Format (IMT): application/pdf
• Access Restrictions: インターネット公開
• Rights (production): 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/.
• Related Material (DOI): 10.1038/s41598-018-28439-1
• Data Provider (Database): 国立情報学研究所 : 学術機関リポジトリデータベース（IRDB）（機関リポジトリ）; https://irdb.nii.ac.jp
• Original Data Provider (Database): 徳島大学 : 徳島大学機関リポジトリ

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