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j.kint.2018.10.017.pdf7.11 MBAdobe PDF見る/開く
タイトル: Myofibroblasts acquire retinoic acid–producing ability during fibroblast-to-myofibroblast transition following kidney injury
著者: Nakamura, Jin
Sato, Yuki
Kitai, Yuichiro
Wajima, Shuichi
Yamamoto, Shinya
Oguchi, Akiko
Yamada, Ryo
Kaneko, Keiichi
Kondo, Makiko
Uchino, Eiichiro
Tsuchida, Junichi
Hirano, Keita
Sharma, Kumar
Kohno, Kenji
Yanagita, Motoko
著者名の別形: 中村, 仁
佐藤, 有紀
北井, 悠一朗
小口, 綾貴子
近藤, 麻紀子
内野, 詠一郎
土田, 潤一
比良野, 圭太
河野, 憲二
柳田, 素子
キーワード: chronic kidney disease
fibroblast
fibrosis
proximal tubule
発行日: 17-Jan-2019
出版者: Elsevier BV
誌名: Kidney International
抄録: Tubular injury and interstitial fibrosis are the hallmarks of chronic kidney disease. While recent studies have verified that proximal tubular injury triggers interstitial fibrosis, the impact of fibrosis on tubular injury and regeneration remains poorly understood. We generated a novel mouse model expressing diphtheria toxin receptor on renal fibroblasts to allow for the selective disruption of renal fibroblast function. Administration of diphtheria toxin induced upregulation of the tubular injury marker Ngal and caused tubular proliferation in healthy kidneys, whereas administration of diphtheria toxin attenuated tubular regeneration in fibrotic kidneys. Microarray analysis revealed down-regulation of the retinol biosynthesis pathway in diphtheria toxin-treated kidneys. Healthy proximal tubules expressed retinaldehyde dehydrogenase 2 (RALDH2), a rate-limiting enzyme in retinoic acid biosynthesis. After injury, proximal tubules lost RALDH2 expression, whereas renal fibroblasts acquired strong expression of RALDH2 during the transition to myofibroblasts in several models of kidney injury. The retinoic acid receptor (RAR) RARγ was expressed in proximal tubules both with and without injury, and αB-crystallin, the product of an RAR target gene, was strongly expressed in proximal tubules after injury. Furthermore, BMS493, an inverse agonist of RARs, significantly attenuated tubular proliferation in vitro. In human biopsy tissue from patients with IgA nephropathy, detection of RALDH2 in the interstitium correlated with older age and lower kidney function. These results suggest a role of retinoic acid signaling and cross-talk between fibroblasts and tubular epithelial cells during tubular injury and regeneration, and may suggest a beneficial effect of fibrosis in the early response to injury.
記述: 腎障害における線維化の正の側面の発見 --線維化が腎臓を修復する--. 京都大学プレスリリース. 2019-01-18.
著作権等: © 2019, International Society of Nephrology. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
URI: http://hdl.handle.net/2433/236048
DOI(出版社版): 10.1016/j.kint.2018.10.017
関連リンク: http://www.kyoto-u.ac.jp/ja/research/research_results/2018/190117_2.html
出現コレクション:学術雑誌掲載論文等

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