※ をクリックすると外部の論文のサイトが開きます。
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
- 巻
- 649
- 号
- 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