ROLE OF GLYCATED ALBUMIN IN DIABETIC NEPHROPATHY

糖化白蛋白在糖尿病肾病中的作用

• 批准号: 6012960
• 负责人: SHELDON CHEN
• 金额: $ 4.17万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-06-01 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6012960
• 关键词: albumins; biological signal transduction; cell line; diabetic nephropathy; glycosylation; pathologic process; protein kinase C; tissue /cell culture; transforming growth factors

DESCRIPTION The mechanisms mediating kidney damage in diabetes stem from chronic hyperglycemia, but the intermediary steps are not completely understood. Evidence is accumulating that non-enzymatic glycosylation of proteins may link high glucose to diabetic kidney injury. Glycated proteins predominantly exist as Amadori products, and glycated albumin (GA) is the most abundant Amador-modified protein in serum. GA causes many of the same alterations in renal physiology as those seen in diabetic nephropathy. Our studies have shown that GA stimulates cultured mouse mesangial cells to produce excess extracellular matrix, a precursor of renal fibrosis that correlates well with decline in kidney function. The cells also make transforming growth factor- beta, a pro-sclerotic cytokine that may mediate the fibrogenic effects of GA. Protein kinase C (PKC) is up-regulated in diabetes and may signal increased mesangial TGF-beta. We hypothesize that GA participates in diabetic nephropathy increased mesangial TGF-beta. We hypothesize that GA participates in diabetic nephropathy by a mechanism that involves PKC as an intracellular signaling system and TGF-beta as a downstream effector of diabetic renal injury. Understanding the pathophysiology may yield now therapies to treat diabetic kidney disease and reduce the incidence of renal failure.

描述介导糖尿病中肾脏损伤的机制源于慢性高血糖，但中介步骤尚未完全了解。有证据表明，蛋白质的非酶糖基化可能将高葡萄糖与糖尿病肾损伤联系起来。糖化蛋白主要作为Amadori产物存在，而糖化白蛋白（GA）是血清中最丰富的Amador修饰蛋白。 GA在肾脏肾病中引起许多肾脏生理学的改变。我们的研究表明，GA刺激培养的小鼠肾小球细胞产生过多的细胞外基质，这是肾纤维化的前体，与肾功能下降良好相关。这些细胞还使转化生长因子β，这是一种促骨质细胞因子，可能介导GA的纤维化作用。蛋白激酶C（PKC）在糖尿病中被上调，并可能信号增加了肾小球TGF-β。我们假设GA参与糖尿病性肾病增加了肾小球的TGF-β。我们假设GA通过涉及PKC作为细胞内信号系统和TGF-β作为糖尿病肾损伤的下游效应的机制参与糖尿病性肾病。现在了解病理生理学可能会产生治疗糖尿病肾脏疾病并减少肾衰竭的疗法。