ROCK Inhibition May Stop Diabetic Kidney Disease

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  • Matoba Keiichiro
    Division of Diabetes, Metabolism, and Endocrinology, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, Japan
  • Takeda Yusuke
    Division of Diabetes, Metabolism, and Endocrinology, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, Japan
  • Nagai Yosuke
    Division of Diabetes, Metabolism, and Endocrinology, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, Japan
  • Kanazawa Yasushi
    Division of Diabetes, Metabolism, and Endocrinology, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, Japan
  • Kawanami Daiji
    Department of Endocrinology and Diabetes Mellitus, Fukuoka University School of Medicine, Fukuoka, Japan
  • Yokota Tamotsu
    Division of Diabetes, Metabolism, and Endocrinology, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, Japan
  • Utsunomiya Kazunori
    Center for Preventive Medicine, The Jikei University School of Medicine, Tokyo, Japan
  • Nishimura Rimei
    Division of Diabetes, Metabolism, and Endocrinology, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, Japan

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<p>Diabetic kidney disease (DKD) is the leading cause of end-stage renal disease and is strongly associated with cardiovascular mortality. Given the pandemic of obesity and diabetes, the elucidation of the molecular underpinnings of DKD and establishment of effective therapy are urgently required. Studies over the past decade have identified the activated renin-angiotensin system (RAS) and hemodynamic changes as important therapeutic targets. However, given the residual risk observed in patients treated with RAS inhibitors and/or sodium glucose co-transporter 2 inhibitors, the involvement of other molecular machinery is likely, and the elucidation of such pathways represents fertile ground for the development of novel strategies. Rho-kinase (ROCK) is a serine/threonine kinase that is under the control of small GTPase protein Rho. Many fundamental cellular processes, including migration, proliferation, and survival are orchestrated by ROCK through a mechanism involving cytoskeletal reorganization. From a pathological standpoint, several analyses provide compelling evidence supporting the hypothesis that ROCK is an important regulator of DKD that is highly pertinent to cardiovascular disease. In cell-based studies, ROCK is activated in response to a diverse array of external stimuli associated with diabetes, and renal ROCK activity is elevated in the context of type 1 and 2 diabetes. Experimental studies have demonstrated the efficacy of pharmacological or genetic inhibition of ROCK in the prevention of diabetes-related histological and functional abnormalities in the kidney. Through a bird's eye view of ROCK in renal biology, the present review provides a conceptual framework that may be widely applicable to the pathological processes of multiple organs and illustrate novel therapeutic promise in diabetology.</p>

収録刊行物

  • JMA Journal

    JMA Journal 3 (3), 154-163, 2020-07-15

    公益社団法人 日本医師会 / 日本医学会

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