349274: Fujita Yui/[冨永辰也]/[安部秀斉]/Kangawa Yumi/Fukushima Naoshi/Ueda Otoya/Jishage Kou-Ichi/[岸誠司]/[村上太一]/Saga Yumiko/Kanwar Yashpal S/[長井幸二郎]/[土井俊夫]/An adjustment in BMP4 function represents a treatment for diabetic nephropathy and podocyte injury./[Scientific Reports]/[冨永辰也]

著作: Fujita Yui/[冨永辰也]/[安部秀斉]/Kangawa Yumi/Fukushima Naoshi/Ueda Otoya/Jishage Kou-Ichi/[岸誠司]/[村上太一]/Saga Yumiko/Kanwar Yashpal S/[長井幸二郎]/[土井俊夫]/An adjustment in BMP4 function represents a treatment for diabetic nephropathy and podocyte injury./[Scientific Reports]/[冨永辰也]

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EID: 349274
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種別

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学術論文(審査論文)

言語

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英語

招待

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審査

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カテゴリ

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共著種別

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学究種別

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組織

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著者

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(英) Fujita Yui

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学籍番号推奨
冨永辰也([徳島大学.大学院医歯薬学研究部.保健学域.保健科学部門.医用検査学系.生体機能解析学])

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学籍番号推奨
安部秀斉

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(英) Kangawa Yumi

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(英) Fukushima Naoshi

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(英) Ueda Otoya

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(英) Jishage Kou-Ichi

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岸誠司

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村上太一

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(英) Saga Yumiko

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貢献度任意

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(英) Kanwar Yashpal S

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長井幸二郎

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土井俊夫

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題名

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(英) An adjustment in BMP4 function represents a treatment for diabetic nephropathy and podocyte injury.

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(日) 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.

キーワード

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発行所

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誌名

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Scientific Reports([Nature Publishing Group])

(eISSN: 2045-2322)

ISSN	任意	2045-2322 ISSN: 2045-2322 (eISSN: 2045-2322) Title: Scientific reports Title(ISO): Sci Rep Publisher: Nature Portfolio (NLM Catalog) (Scopus) (CrossRef) (Scopus information is found. [need login])

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号

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---

都市

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年月日

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2018年 8月 29日

URL

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DOI

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10.1038/s41598-018-31464-9 (→Scopusで検索)

PMID

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30158674 (→Scopusで検索)

CRID

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被引用数

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指導教員

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冨永辰也([徳島大学.大学院医歯薬学研究部.保健学域.保健科学部門.医用検査学系.生体機能解析学])

備考

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(英) PublicationType: Journal Article

徳島大学教育・研究者情報データベース(EDB)

Education and Research Database (EDB), Tokushima University