Diabetic Nephropathy is associated with gene expression levels of oxidative phosphorylation and related pathways
Diabetic Nephropathy is associated with gene expression levels of oxidative phosphorylation and related pathways
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DOI：
10.2337/db05-1438
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发表时间：
2006-06-01
期刊：
影响因子：
7.7
通讯作者：
Mauer, Michael
中科院分区：
文献类型：
--
作者：
Huang, Chunmei;Kim, Youngki;Mauer, Michael
糖尿病肾病患者皮肤成纤维细胞的体外行为与糖尿病肾病风险相关。在这里，我们比较了两组1型糖尿病患者的皮肤成纤维细胞基因表达谱：20例糖尿病肾病病变发展速度非常快（“快速通道”）与20例糖尿病肾病病变发展速度非常慢（“慢速通道”）。使用Affymetrix HG-U133 A GeneChips评估在25 mmol/l葡萄糖中生长36小时的皮肤成纤维细胞的基因表达谱，以确定给定生物途径中在组差异方面方向一致的基因比例。有5条通路具有统计学意义。在快速通道组中，所有人都有显著更高比例的基因表达水平更高。这些途径包括氧化磷酸化（P < 0.001）、电子传递系统复合物III（P = 0.017）、柠檬酸循环（P = 0.037）、丙酸代谢（P = 0.044）和转录因子（P = 0.046），其中前四个途径密切相关并具有重叠基因。这些结果支持了氧化磷酸化和相关的上游途径可能在糖尿病肾病的发病机制中起重要作用的概念。这些发现是否反映了固有的遗传细胞特征，“细胞记忆”，或两者都需要进一步研究。
The in vitro behavior of skin fibroblasts from patients with or without diabetic nephropathy is associated with diabetic nephropathy risk. Here we compared skin fibroblast gene expression profiles from two groups of type 1 diabetic patients: 20 with very fast ("fast-track") versus 20 with very slow ("slow-track") rates of development of diabetic nephropathy lesions. Gene expression profiles of skin fibroblasts grown in 25 mmol/l glucose for 36 h were assessed by Affymetrix HG-U133A GeneChips to determine the proportion of genes in a given biological pathway that were directionally consistent in their group differences. Five pathways reached statistical significance. All had significantly greater proportions of genes with higher expression levels in the fast-track group. These pathways, the first four of which are closely related and have overlapping genes, included oxidative phosphorylation (P < 0.001), electron transport system complex III (P = 0.017), citrate cycle (P = 0.037), propanoate metabolism (P = 0.044), and transcription factors (P = 0.046). These results support the concept that oxidative phosphorylation and related upstream pathways may be important in the pathogenesis of diabetic nephropathy. Whether these findings reflect inherent genetic cellular characteristics, "cell memory," or both requires further study.