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ID 110997
Title Alternative
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
Author
Araki, Makoto 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
Keywords
Glomerulonephritis
Glomerulosclerosis
Collagen type IV
Smad1
Content Type
Thesis or Dissertation
Description
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.
Journal Title
Scientific Reports
ISSN
20452322
Publisher
Springer nature
Volume
6
Start Page
31216
Published Date
2016-08-05
Remark
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。
Rights
© 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/
EDB ID
DOI (Published Version)
URL ( Publisher's Version )
FullText File
language
eng
TextVersion
ETD
MEXT report number
乙第2098号
Diploma Number
乙医第1752号
Granted Date
2017-11-30
Degree Name
Doctor of Medical Science
Grantor
Tokushima University
departments
Medical Sciences