※ 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-associated, coiled-coil-containing protein kinase 1 regulates development of diabetic kidney disease via modulation of fatty acid metabolism.
- 参照URL
- https://researchmap.jp/351K/published_papers/37931137
- 著者
- 著者（英）
- Yosuke Nagai,Keiichiro Matoba,Yusuke Takeda,Hideji Yako,Tomoyo Akamine,Kensuke Sekiguchi,Yasushi Kanazawa,Tamotsu Yokota,Kazunori Sango,Daiji Kawanami,Kazunori Utsunomiya,Rimei Nishimura
- 担当区分
- 概要
- 概要（英）
- Dysregulation of fatty acid utilization is increasingly recognized as a significant component of diabetic kidney disease. Rho-associated, coiled-coil-containing protein kinase (ROCK) is activated in the diabetic kidney, and studies over the past decade have illuminated ROCK signaling as an essential pathway in diabetic kidney disease. Here, we confirmed the distinct role of ROCK1, an isoform of ROCK, in fatty acid metabolism using glomerular mesangial cells and ROCK1 knockout mice. Mesangial cells with ROCK1 deletion were protected from mitochondrial dysfunction and redox imbalance driven by transforming growth factor β, a cytokine upregulated in diabetic glomeruli. We found that high-fat diet-induced obese ROCK1 knockout mice exhibited reduced albuminuria and histological abnormalities along with the recovery of impaired fatty acid utilization and mitochondrial fragmentation. Mechanistically, we found that ROCK1 regulates the induction of critical mediators in fatty acid metabolism, including peroxisome proliferator-activated receptor gamma coactivator 1α, carnitine palmitoyltransferase 1, and widespread program-associated cellular metabolism. Thus, our findings highlight ROCK1 as an important regulator of energy homeostasis in mesangial cells in the overall pathogenesis of diabetic kidney disease.
- 出版者・発行元
- 出版者・発行元（英）
- 誌名
- 誌名（英）
- Kidney international
- 巻
- 号
- 開始ページ
- 終了ページ
- 出版年月
- 2022年5月18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.kint.2022.04.021
- 共同研究・競争的資金等の研究課題