Fang Tingting, Ma Congcong, Zhang Zhanming, Sun Luning, Zheng Ningning
Department of Pathophysiology, College of Basic Medical Science, China Medical University, Shenyang, Liaoning, China.
Pharmaceutical Sciences, China Medical University-The Queen's University of Belfast Joint College, Shenyang, Liaoning, China.
Front Pharmacol. 2023 Feb 10;14:1088288. doi: 10.3389/fphar.2023.1088288. eCollection 2023.
Diabetes mellitus (DM) is a group of metabolic diseases caused by absolute or relative deficiency of insulin secretion and characterized by chronic hyperglycemia. Its complications affect almost every tissue of the body, usually leading to blindness, renal failure, amputation, etc. and in the final stage, it mostly develops into cardiac failure, which is the main reason why diabetes mellitus manifests itself as a high clinical lethality. The pathogenesis of diabetes mellitus and its complications involves various pathological processes including excessive production of mitochondrial reactive oxygen species (ROS) and metabolic imbalance. Hypoxia-inducible Factor (HIF) signaling pathway plays an important role in both of the above processes. Roxadustat is an activator of Hypoxia-inducible Factor-1α, which increases the transcriptional activity of Hypoxia-inducible Factor-1α by inhibiting hypoxia-inducible factor prolyl hydroxylase (HIF-PHD). Roxadustat showed regulatory effects on maintaining metabolic stability in the hypoxic state of the body by activating many downstream signaling pathways such as vascular endothelial growth factor (VEGF), glucose transporter protein-1 (GLUT1), lactate dehydrogenase (LDHA), etc. This review summarizes the current research findings of roxadustat on the diseases of cardiomyopathy, nephropathy, retinal damage and impaired wound healing, which also occur at different stages of diabetes and greatly contribute to the damage caused by diabetes to the organism. We attempts to uncover a more comprehensive picture of the therapeutic effects of roxadustat, and inform its expanding research about diabetic complications treatment.
糖尿病(DM)是一组由胰岛素分泌绝对或相对不足引起的代谢性疾病,其特征为慢性高血糖。其并发症几乎影响身体的每个组织,通常导致失明、肾衰竭、截肢等,在疾病后期大多发展为心力衰竭,这也是糖尿病具有高临床致死率的主要原因。糖尿病及其并发症的发病机制涉及多种病理过程,包括线粒体活性氧(ROS)产生过多和代谢失衡。缺氧诱导因子(HIF)信号通路在上述两个过程中均起重要作用。罗沙司他是缺氧诱导因子-1α的激活剂,它通过抑制缺氧诱导因子脯氨酰羟化酶(HIF-PHD)来增加缺氧诱导因子-1α的转录活性。罗沙司他通过激活血管内皮生长因子(VEGF)、葡萄糖转运蛋白-1(GLUT1)、乳酸脱氢酶(LDHA)等多种下游信号通路,对维持机体缺氧状态下的代谢稳定性具有调节作用。本综述总结了罗沙司他目前在心肌病、肾病、视网膜损伤和伤口愈合受损等疾病方面的研究结果,这些疾病也发生在糖尿病的不同阶段,对糖尿病给机体造成的损害有很大影响。我们试图揭示罗沙司他治疗效果的更全面情况,并为其在糖尿病并发症治疗方面的拓展研究提供信息。
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