Greven Wendela L, Waanders Femke, Nagai Ryoji, van den Heuvel Marius C, Navis Gerjan, van Goor Harry
Department of Pathology and Laboratory Medicine, and Department of Nephrology, University Medical Center Groningen, Groningen, The Netherlands.
Kidney Int. 2005 Aug;68(2):595-602. doi: 10.1111/j.1523-1755.2005.00437.x.
Advanced glycation end products (AGEs) contribute to diabetic and atherosclerotic end-organ damage, but the mechanisms of AGE-formation and AGE-induced damage are unclear. Glycolaldehyde (GA) is a Maillard-reaction intermediate and can be formed by reaction of L-serine with the myeloperoxidase-system. GA reacts with proteins to form AGEs, such as GA-pyridine, which is specific for protein modification by GA. GA-pyridine accumulates in human atherosclerotic lesions. As atherosclerosis and progressive glomerulosclerosis share many similarities, we hypothesized that GA-pyridine accumulates in renal diseases, especially those with prominent mesangial involvement.
Paraffin-embedded renal biopsies from 55 patients with various renal diseases, as well as control tissue, obtained from the unaffected part of kidneys from 10 patients with renal cell carcinoma were immunohistochemically stained with a monoclonal antibody directed against GA-pyridine and were scored semiquantitatively. Additional sections were scored for mesangial matrix expansion (MME) and focal glomerular sclerosis (FGS).
In normal human kidneys, GA-pyridine was mainly localized in tubular epithelial cells, but not in the glomerular mesangium. Significant mesangial GA-pyridine accumulation was found in disorders with mesangial involvement as a common denominator. In contrast, mesangial GA-pyridine accumulation was less prominent in renal diseases without prominent mesangial involvement. Moreover, mesangial GA-pyridine accumulation was more pronounced in kidneys with higher MME and FGS scores across the different diagnoses.
GA-pyridine accumulates in the mesangium in human renal disease, in particular in disorders with mesangial involvement. Further studies should elucidate whether mesangial GA-pyridine plays a role in the progression of glomerular damage.
晚期糖基化终产物（AGEs）会导致糖尿病和动脉粥样硬化性终末器官损伤，但AGE形成及AGE诱导损伤的机制尚不清楚。乙醇醛（GA）是美拉德反应的中间体，可由L-丝氨酸与髓过氧化物酶系统反应形成。GA与蛋白质反应形成AGEs，如GA-吡啶，它是GA对蛋白质修饰的特异性产物。GA-吡啶在人类动脉粥样硬化病变中蓄积。由于动脉粥样硬化和进行性肾小球硬化有许多相似之处，我们推测GA-吡啶在肾脏疾病中蓄积，尤其是那些系膜受累明显的疾病。
对55例患有各种肾脏疾病患者的石蜡包埋肾活检组织以及取自10例肾细胞癌患者肾脏未受影响部位的对照组织，用针对GA-吡啶的单克隆抗体进行免疫组织化学染色，并进行半定量评分。对额外切片进行系膜基质扩张（MME）和局灶性肾小球硬化（FGS）评分。
在正常人类肾脏中，GA-吡啶主要定位于肾小管上皮细胞，而不在肾小球系膜中。在以系膜受累为共同特征的疾病中发现有明显的系膜GA-吡啶蓄积。相比之下，在系膜受累不明显的肾脏疾病中，系膜GA-吡啶蓄积不那么突出。此外，在不同诊断中，MME和FGS评分较高的肾脏中，系膜GA-吡啶蓄积更明显。
GA-吡啶在人类肾脏疾病的系膜中蓄积，尤其是在系膜受累的疾病中。进一步研究应阐明系膜GA-吡啶是否在肾小球损伤进展中起作用。
