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

• Material Type: 博士論文
• ISSN: 2045-2322
• Title: Novel Interplay Between Smad1 and Smad3 Phosphorylation via AGE Regulates the Progression of Diabetic Nephropathy
• Volume: 8
• 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
• Degree grantor/type: 徳島大学
• Date Granted: 2018-09-27
• Date Granted (W3CDTF): 2018-09-27
• Dissertation Number: 甲第3216号
• Degree Type: 博士（医学）
• Conferring No. (Dissertation): 甲第3216号
• 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.
• DOI: info:doi/10.1038/s41598-018-28439-1; https://doi.org/info:doi/10.1038/s41598-018-28439-1
• Persistent ID (NDL): info:ndljp/pid/11217338; https://dl.ndl.go.jp/pid/11217338
• Collection: 障害者向け資料
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• Collection (particular): 国立国会図書館デジタルコレクション > デジタル化資料 > 博士論文; https://dl.ndl.go.jp/collections/A00014
• Acquisition Basis: 博士論文（自動収集）
• Date Accepted (W3CDTF): 2019-01-04T08:16:43+09:00
• Format (IMT): application/pdf
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• Periodical Title (URI): http://repo.lib.tokushima-u.ac.jp/112878
• Data Provider (Database): 国立国会図書館 : 国立国会図書館デジタルコレクション; https://dl.ndl.go.jp