ID | 110997 |
タイトル別表記 | Smad1の条件付き遺伝子削除は進行性糸球体腎炎による糸球体傷害を改善する
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著者 |
荒木, 真
Kyoto University|Tokushima University
Matsubara, Takeshi
Kyoto University
Torikoshi, Kazuo
Kyoto University
Iehara, Noriyuki
Kyoto University
Fukatsu, Atsushi
Kyoto University
Kita, Toru
Kobe City Medical Center General Hospital
Arai, Hidenori
National Center for Geriatrics and Gerontology
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キーワード | Glomerulonephritis
Glomerulosclerosis
Collagen type IV
Smad1
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資料タイプ |
学位論文
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抄録 | Matrix expansion and cell proliferation are concomitantly observed in various glomerular injuries. However, the molecular mechanisms responsible for these changes have not been fully elucidated. We have reported that Smad1 is a key signalling molecule that regulates the transcription of type IV collagen (Col4) in mesangial matrix expansion and is thereby involved in glomerular injury in an acute model of glomerulonephritis. In this study, we addressed the role of Smad1 signalling in accelerated nephrotoxic nephritis (NTN), a model of progressive glomerulonephritis, using conditional deletion of Smad1 in Rosa26CreERT2 mice (Smad1-CKO). Mesangial matrix expansion in the Smad1-CKO mice with NTN was significantly inhibited compared with that in wild type mice with NTN, which was consistent with the decrease in Col4 expression level. On the other hand, STAT3 activation and cell proliferation were not influenced by Smad1 deletion in the NTN model. Therefore, we investigated another factor that activates cell proliferation in the absence of Smad1. Id2 induced VEGF secretion and subsequent STAT3 activation, independently of Smad1 expression in mouse mesangial cells. Here we show that Smad1 plays an important role in the development of glomerular injury without affecting cell proliferation, in progressive glomerulonephritis.
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掲載誌名 |
Scientific Reports
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ISSN | 20452322
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出版者 | Springer nature
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巻 | 6
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開始ページ | 31216
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発行日 | 2016-08-05
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備考 | 内容要旨・審査要旨・論文本文の公開
本論文は, 著者Makoto Araki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 | © The Author(s) 2016. This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
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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
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著者版フラグ |
博士論文全文を含む
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文科省報告番号 | 乙第2098号
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学位記番号 | 乙医第1752号
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学位授与年月日 | 2017-11-30
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学位名 |
博士(医学)
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学位授与機関 |
徳島大学
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部局 |
医学系
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