Lagranha Claudia J, Fiorino Patricia, Casarini Dulce Elena, Schaan Beatriz D'Agord, Irigoyen Maria Claudia
Laboratório de Hipertensão Experimental, Unidade de Hipertensão, Instituto do Coração, HC-FMUSP, São Paulo.
Arq Bras Endocrinol Metabol. 2007 Aug;51(6):901-12. doi: 10.1590/s0004-27302007000600003.
The determinant of the diabetic nephropathy is hyperglycemia, but hypertension and other genetic factors are also involved. Glomerulus is the focus of the injury, where mesangial cell proliferation and extracellular matrix occur because of the increase of the intra- and extracellular glucose concentration and overexpression of GLUT1. Sequentially, there are increases in the flow by the poliol pathway, oxidative stress, increased intracellular production of advanced glycation end products (AGEs), activation of the PKC pathway, increase of the activity of the hexosamine pathway, and activation of TGF-beta1. High glucose concentrations also increase angiotensin II (AII) levels. Therefore, glucose and AII exert similar effects in inducing extracellular matrix formation in the mesangial cells, using similar transductional signal, which increases TGF-beta1 levels. In this review we focus in the effect of glucose and AII in the mesangial cells in causing the events related to the genesis of diabetic nephropathy. The alterations in the signal pathways discussed in this review give support to the observational studies and clinical assays, where metabolic and antihypertensive controls obtained with angiotensin-converting inhibitors have shown important and additive effect in the prevention of the beginning and progression of diabetic nephropathy. New therapeutic strategies directed to the described intracellular events may give future additional benefits.
糖尿病肾病的决定因素是高血糖，但高血压和其他遗传因素也有影响。肾小球是损伤的焦点，由于细胞内和细胞外葡萄糖浓度增加以及GLUT1的过度表达，系膜细胞会发生增殖和细胞外基质改变。随后，多元醇途径流量增加、氧化应激、细胞内晚期糖基化终产物（AGEs）生成增加、PKC途径激活、己糖胺途径活性增加以及TGF-β1激活。高血糖浓度还会增加血管紧张素II（AII）水平。因此，葡萄糖和AII利用相似的转导信号在诱导系膜细胞细胞外基质形成方面发挥相似作用，这会增加TGF-β1水平。在本综述中，我们重点关注葡萄糖和AII对系膜细胞的影响，这些影响导致了与糖尿病肾病发生相关的事件。本综述中讨论的信号通路改变为观察性研究和临床检测提供了支持，在这些研究中，使用血管紧张素转换酶抑制剂进行代谢和抗高血压控制已显示出在预防糖尿病肾病的发生和进展方面具有重要的累加效应。针对上述细胞内事件的新治疗策略可能会带来更多益处。
