title: Diabetic nephropathy is associated with gene expression levels of oxidative phosphorylation and related pathways.
abstract: 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.
authors.affiliation: Department of Pediatrics, University of Minnesota Medical School, Minneapolis, Minnesota, USA.
authors.forename: Chunmei
authors.initials: C
authors.lastname: Huang
authors.forename: Youngki
authors.initials: Y
authors.lastname: Kim
authors.forename: M Luiza
authors.initials: ML
authors.lastname: Caramori
authors.forename: Jason H
authors.initials: JH
authors.lastname: Moore
authors.forename: Stephen S
authors.initials: SS
authors.lastname: Rich
authors.forename: Josyf C
authors.initials: JC
authors.lastname: Mychaleckyj
authors.forename: Paul C
authors.initials: PC
authors.lastname: Walker
authors.forename: Michael
authors.initials: M
authors.lastname: Mauer
mesh_terms: D000328:Adult; D002478:Cells, Cultured; D003928:Diabetic Nephropathies / Q000235:genetics*; D004579:Electron Transport; D005260:Female; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D020869:Gene Expression Profiling; D006801:Humans; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D020411:Oligonucleotide Array Sequence Analysis; D010085:Oxidative Phosphorylation; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000235:genetics*; D012867:Skin / Q000166:cytology; D014157:Transcription Factors / Q000235:genetics
chemical_list: D014157:Transcription Factors