アクセス数 : ?
ダウンロード数 : ?
ID 112896
タイトル別表記
BMP4の機能調節は糖尿病性腎症及びポドサイト障害の治療につながる
著者
藤田, 結衣 徳島大学大学院医科学教育部(医学専攻)
Kangawa, Yumi Tokushima University
Fukushima, Naoshi Chugai Pharmaceutical Co., Ltd
Ueda, Otoya Chugai Pharmaceutical Co., Ltd
Jishage, Kou-ichi Chugai Pharmaceutical Co., Ltd|Chugai Research Institute for Medical Science Inc.
Saga, Yumiko National Institute of Genetics
Kanwar, Yashpal S. Northwestern University
キーワード
Podocyte
cytokine
diabetic nephropathy
BMP4
CKD
資料タイプ
学位論文
抄録
Podocyte injury has been proposed to play an important role in diabetic nephropathy; however, its pathological mechanism remains unclear. We have shown that bone morphogenetic protein 4 (BMP4) signaling leads to the glomerular changes characteristic of this disorder. To analyze the molecular mechanism of podocyte injury, the effect of BMP4 was investigated using streptozotocin (STZ)- induced, Bmp4 heterozygous knockout (Bmp4+/−) and podocyte-specific Bmp4 knockout mice. Mice with STZ-induced diabetes exhibited glomerular matrix hyperplasia and decreased numbers of podocyte nucleus-specific WT1-positive cells. The number of podocytes and proteinuria were improved in both diabetic Bmp4 knockout mouse models compared to the effects observed in the control mice. The effect of BMP4 overexpression on Bmp4-induced or podocyte-specific transgenic mice was examined. Tamoxifen-induced Bmp4-overexpressing mice exhibited mesangial matrix expansion and decreased numbers of WT1-positive cells. Podocyte-specific Bmp4-overexpressing mice displayed increased kidney BMP4 expression and mesangial matrix expansion but decreased nephrin expression and numbers of WT1-positive cells. Both lines of Bmp4-overexpressing mice exhibited increased albuminuria. In cultured podocytes, BMP4 increased phospho-p38 levels. BMP4 decreased nephrin expression but increased cleaved caspase-3 levels. p38 suppression inhibited caspase-3 activation. Apoptosis was confirmed in STZ-diabetic glomeruli and Bmp4-overexpressing mice. Bmp4 +/− mice with diabetes displayed reduced apoptosis. Based on these data, the BMP4 signaling pathway plays important roles in the development of both podocyte injury and mesangial matrix expansion in diabetic nephropathy.
掲載誌名
Scientific Reports
ISSN
20452322
出版者
Springer Nature
8
開始ページ
13011
発行日
2018-08-29
備考
内容要旨・審査要旨・論文本文の公開
本論文は, 著者Yui Fujita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) 2018 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3240号
学位記番号
甲医第1389号
学位授与年月日
2018-10-25
学位名
博士(医学)
学位授与機関
徳島大学
部局
医学系
病院