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生长激素(GH)、胰岛素样生长因子(IGFs)和血管内皮生长因子(VEGF)在糖尿病肾病中的作用。

The involvement of growth hormone (GH), insulin-like growth factors (IGFs) and vascular endothelial growth factor (VEGF) in diabetic kidney disease.

作者信息

Flyvbjerg Allan, Khatir Dinah S, Jensen Louise J N, Dagnaes-Hansen Frederik, Gronbaek Henning, Rasch Ruth

机构信息

Medical Department M (Diabetes and Endocrinology), Aarhus University Hospital, DK-8000 Aarhus C, Denmark.

出版信息

Curr Pharm Des. 2004;10(27):3385-94. doi: 10.2174/1381612043383106.

Abstract

At present, diabetic kidney disease affects about 15-25 % of patients with type 1 diabetes (T1D) and 30-40 % of patients with type 2 diabetes (T2D). Several decades of extensive research have elucidated various pathways to be implicated in the development of diabetic kidney disease. These include metabolic factors beyond blood glucose (e.g. advanced glycation endproducts (AGEs)), haemodynamic factors (e.g. the renin angiotensin system (RAS)), intracellular signaling molecule proteins (e.g. protein kinase C (PKC)) and growth factors/cytokines (e.g. growth hormone (GH), insulin-like growth factors (IGFs), transforming growth factor beta (TGF-beta) and vascular endothelial growth factor (VEGF)). This review focuses on the role of three of these growth factors, i.e. GH, IGFs and VEGF. A brief discussion of each system is followed by description of its expression in the normal kidney. Then, for each system, in vitro, experimental and clinical evidence addressing the role of the system in diabetic kidney disease is presented. The interplay of each system to other potential pathways will also be addressed. Finally, well-known and potential therapeutic strategies targeting the GH/IGF and VEGF systems in a specific or indirect way will discussed.

摘要

目前,糖尿病肾病影响着约15% - 25%的1型糖尿病(T1D)患者以及30% - 40%的2型糖尿病(T2D)患者。数十年的广泛研究阐明了糖尿病肾病发生发展过程中涉及的多种途径。这些途径包括血糖以外的代谢因素(如晚期糖基化终产物(AGEs))、血流动力学因素(如肾素血管紧张素系统(RAS))、细胞内信号分子蛋白(如蛋白激酶C(PKC))以及生长因子/细胞因子(如生长激素(GH)、胰岛素样生长因子(IGFs)、转化生长因子β(TGF-β)和血管内皮生长因子(VEGF))。本综述重点关注其中三种生长因子,即GH、IGFs和VEGF的作用。在简要讨论每个系统之后,描述其在正常肾脏中的表达情况。然后,针对每个系统,分别呈现其在糖尿病肾病中作用的体外、实验和临床证据。还将探讨每个系统与其他潜在途径之间的相互作用。最后,将讨论以特定或间接方式靶向GH/IGF和VEGF系统的知名及潜在治疗策略。

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