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論文
タイトル
タイトル(英)
Rho-kinase inhibitor restores glomerular fatty acid metabolism in diabetic kidney disease.
参照URL
https://researchmap.jp/351K/published_papers/41342761
著者
著者(英)
Yosuke Nagai,Keiichiro Matoba,Hideji Yako,Shinji Ohashi,Kensuke Sekiguchi,Etsuko Mitsuyoshi,Kazunori Sango,Daiji Kawanami,Kazunori Utsunomiya,Rimei Nishimura
担当区分
概要
概要(英)
The small GTPase Rho and its effector Rho-kinase (ROCK) are activated in the diabetic kidney, and recent studies decade have demonstrated that ROCK signaling is an integral pathway in the progression of diabetic kidney disease. We previously identified the distinct role of ROCK1, an isoform of ROCK, in fatty acid metabolism in diabetic glomeruli. However, the effect of pharmacological intervention for ROCK1 is not clear. In the present study, we show that the inhibition of ROCK1 by Y-27632 and fasudil restores fatty acid oxidation in the glomeruli. Mechanistically, these compounds optimize fatty acid utilization and redox balance in mesangial cells via AMPK phosphorylation and the subsequent induction of PGC-1α. A further in vivo study showed that the inhibition of ROCK1 suppressed the downregulation of the fatty acid oxidation-related gene expression in glomeruli and mitochondrial fragmentation in the mesangial cells of db/db mice. These observations indicate that ROCK1 could be a promising therapeutic target for diabetic kidney disease through a mechanism that improves glomerular fatty acid metabolism.
出版者・発行元
出版者・発行元(英)
誌名
誌名(英)
Biochemical and biophysical research communications
649
開始ページ
32
終了ページ
38
出版年月
2023年1月31日
査読の有無
招待の有無
掲載種別
研究論文(学術雑誌)
ISSN
DOI URL
https://doi.org/10.1016/j.bbrc.2023.01.088
共同研究・競争的資金等の研究課題
研究者
三五 一憲 (サンゴ カズノリ) , 八子 英司 (ヤコ ヒデジ)