An adjustment in BMP4 function represents a treatment for diabetic nephropathy and podocyte injury

• Material Type: 博士論文
• Title: An adjustment in BMP4 function represents a treatment for diabetic nephropathy and podocyte injury
• Author/Editor: Fujita, Yui; Tominaga, Tatsuya; Abe, Hideharu; Kangawa, Yumi; Fukushima, Naoshi; Ueda, Otoya; Jishage, Kou-ichi; Kishi, Seiji; Murakami, Taichi; Saga, Yumiko; Kanwar, Yashpal S.; Nagai, Kojiro; Doi, Toshio
• Author Heading: Fujita, Yui; Tominaga, Tatsuya; Abe, Hideharu; Kangawa, Yumi; Fukushima, Naoshi; Ueda, Otoya; Jishage, Kou-ichi; Kishi, Seiji; Murakami, Taichi; Saga, Yumiko; Kanwar, Yashpal S.; Nagai, Kojiro; Doi, Toshio
• Publication, Distribution, etc.: Springer Nature
• Publication Date: 2018-08-29
• Publication Date (W3CDTF): 2018-08-29
• Alternative Title: 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
• Periodical title: Scientific Reports
• No. or year of volume/issue: 8
• Volume: 8
• Pages: 13011-
• ISSN (Periodical Title): ISSN : 2045-2322
• Degree grantor/type: 徳島大学
• Date Granted: 2018-10-25
• Dissertation Number: 甲第3240号
• Degree Type: 博士（医学）
• Text Language Code: eng
• Subject Heading: Podocyte; cytokine; diabetic nephropathy; BMP4; CKD
• Target Audience: 一般
• Note (General): 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.
• Format (IMT): application/pdf
• Access Restrictions: インターネット公開
• Rights (production): © 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/.
• Related Material (DOI): 10.1038/s41598-018-31464-9
• 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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