Department of Medical Physics, Marian Smoluchowski Institute of Physics, Faculty of Physics, Astronomy and Applied Computer Science, Jagiellonian University, Kraków, Poland.
Clinical Department of Interventional Cardiology, John Paul II Hospital, Kraków, Poland.
Expert Rev Mol Med. 2019 Dec 4;21:e7. doi: 10.1017/erm.2019.8.
Diabetes mellitus (DM) is the most common metabolic disease. A WHO report from 2016 indicates that 422 million people worldwide suffer from DM or hyperglycaemia because of impaired glucose metabolism. Chronic hyperglycaemia leads to micro- and macrovessel damage, which may result in life-threatening complications. The Wnt pathway regulates cell proliferation and survival by modulating the expression of genes that control cell differentiation. Three linked Wnt pathways have been discovered thus far: a β-catenin-dependent pathway and two pathways independent of β-catenin - the planar cell polarity pathway and calcium-dependent pathway. The Wnt pathway regulates genes associated with inflammation, cell cycle, angiogenesis, fibrinolysis and other molecular processes.
This review presents the current state of knowledge regarding the contribution of the Wnt pathway to endothelial ageing under hyperglycaemic conditions and provides new insights into the molecular basis of diabetic endothelial dysfunction.
The β-catenin-dependent pathway is a potential target in the prophylaxis and treatment of early-stage diabetes-related vascular complications. However, the underlying molecular mechanisms remain largely undetermined and require further investigation.
糖尿病(DM)是最常见的代谢疾病。2016 年世界卫生组织的一份报告显示,全球有 4.22 亿人患有 DM 或因葡萄糖代谢受损而出现高血糖。慢性高血糖会导致微血管和大血管损伤,从而导致危及生命的并发症。Wnt 通路通过调节控制细胞分化的基因的表达来调节细胞增殖和存活。迄今为止,已经发现了三种关联的 Wnt 通路:β-连环蛋白依赖性通路和两种不依赖β-连环蛋白的通路——平面细胞极性通路和钙依赖性通路。Wnt 通路调节与炎症、细胞周期、血管生成、纤溶等分子过程相关的基因。
本文综述了目前关于 Wnt 通路在高血糖条件下内皮细胞衰老中的作用的知识状况,并为糖尿病内皮功能障碍的分子基础提供了新的见解。
β-连环蛋白依赖性通路是预防和治疗早期糖尿病相关血管并发症的潜在靶点。然而,其潜在的分子机制在很大程度上仍未确定,需要进一步研究。