『徳島大学 教育・研究者情報データベース (EDB)』---[学外] /
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種別 (必須): 学術論文 (審査論文) [継承]
言語 (必須): 英語 [継承]
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著者 (必須): 1.田蒔 昌憲 ([徳島大学.病院.先端医科医療開発研究プロジェクト]/[徳島大学.病院.中央診療施設等.検査部]/[徳島大学.病院.診療科.内科.腎臓内科])
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2.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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3. (英) Fujita Yui (日) (読)
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4. (英) Koezuka Yasuhiko (日) (読)
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5. (英) Ichien Go (日) (読)
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6.村上 太一
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7.岸 誠司
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8. (英) Yamamoto Keiichi (日) (読)
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9.安部 秀斉
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10.長井 幸二郎
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11.土井 俊夫
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題名 (必須): (英) All-trans retinoic acid suppresses bone morphogenetic protein 4 in mouse diabetic nephropathy through a unique retinoic acid response element.  (日)    [継承]
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要約 (任意): (英) Diabetic nephropathy (DN) causes mesangial matrix expansion, which results in glomerulosclerosis and renal failure. Collagen IV (COL4) is a major component of the mesangial matrix that is positively regulated by bone morphogenetic protein 4 (BMP4)/suppressor of mothers against decapentaplegic (Smad1) signaling. Because previous studies showed that retinoids treatment had a beneficial effect on kidney disease, we investigated the therapeutic potential of retinoids in DN, focusing especially on the regulatory mechanism of BMP4. Diabetes was induced with streptozotocin in 12-wk-old male Crl:CD1(ICR) mice, and, 1 mo later, we initiated intraperitoneal injection of all-trans retinoic acid (ATRA) three times weekly. Glomerular matrix expansion, which was associated with increased BMP4, phosphorylated Smad1, and COL4 expression, worsened in diabetic mice at 24 wk of age. ATRA administration alleviated DN and downregulated BMP4, phosopho-Smad1, and COL4. In cultured mouse mesangial cells, treatment with ATRA or a retinoic acid receptor-α (RARα) agonist significantly decreased BMP4 and COL4 expression. Genomic analysis suggested two putative retinoic acid response elements (RAREs) for the mouse Bmp4 gene. Chromatin immunoprecipitation analysis and reporter assays indicated a putative RARE of the Bmp4 gene, located 11,488-11,501 bp upstream of exon 1A and bound to RARα and retinoid X receptor (RXR), which suppressed BMP4 expression after ATRA addition. ATRA suppressed BMP4 via binding of a RARα/RXR heterodimer to a unique RARE, alleviating glomerular matrix expansion in diabetic mice. These findings provide a novel regulatory mechanism for treatment of DN.  (日)    [継承]
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誌名 (必須): American Journal of Physiology, Endocrinology and Metabolism ([アメリカ生理学会])
(pISSN: 0193-1849, eISSN: 1522-1555)

ISSN (任意): 1522-1555
ISSN: 0193-1849 (pISSN: 0193-1849, eISSN: 1522-1555)
Title: American journal of physiology. Endocrinology and metabolism
Title(ISO): Am J Physiol Endocrinol Metab
Publisher: American Physiological Society
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(必須): 316 [継承]
(必須): 3 [継承]
(必須): E418 E431 [継承]
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年月日 (必須): 西暦 2019年 1月 2日 (平成 31年 1月 2日) [継承]
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DOI (任意): 10.1152/ajpendo.00218.2018    (→Scopusで検索) [継承]
PMID (任意): 30601699    (→Scopusで検索) [継承]
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備考 (任意): 1.(英) PublicationType: Journal Article  (日)    [継承]

標準的な表示

和文冊子 ● Masanori Tamaki, Tatsuya Tominaga, Yui Fujita, Yasuhiko Koezuka, Go Ichien, Taichi Murakami, Seiji Kishi, Keiichi Yamamoto, Hideharu Abe, Kojiro Nagai and Toshio Doi : All-trans retinoic acid suppresses bone morphogenetic protein 4 in mouse diabetic nephropathy through a unique retinoic acid response element., American Journal of Physiology, Endocrinology and Metabolism, Vol.316, No.3, E418-E431, 2019.
欧文冊子 ● Masanori Tamaki, Tatsuya Tominaga, Yui Fujita, Yasuhiko Koezuka, Go Ichien, Taichi Murakami, Seiji Kishi, Keiichi Yamamoto, Hideharu Abe, Kojiro Nagai and Toshio Doi : All-trans retinoic acid suppresses bone morphogenetic protein 4 in mouse diabetic nephropathy through a unique retinoic acid response element., American Journal of Physiology, Endocrinology and Metabolism, Vol.316, No.3, E418-E431, 2019.

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