Faculty Collaboration Database

Effect of high glucose on gene expression in mesangial cells: upregulation of the thiol pathway is an adaptational response. Physiol Genomics 2004 May 19;17(3):271-82

Date

03/25/2004

Pubmed ID

15039483

DOI

10.1152/physiolgenomics.00031.2004

Scopus ID

2-s2.0-3042808652 (requires institutional sign-in at Scopus site)   42 Citations

Abstract

Pathological alterations in glomerular mesangial cells play a critical role in the development of diabetic nephropathy, the leading cause of end-stage renal disease. Molecular mechanisms mediating such alterations, however, remain to be fully understood. The present study first examined the effect of high glucose on the mRNA expression profile in rat mesangial cells using cDNA microarray. Based on variation-weighted criteria and with a false discovery rate of 4.3%, 459 of 17,664 cDNA elements examined were found to be upregulated and 151 downregulated by exposure to 25 mM d-glucose for 5 days. A large number of differentially expressed genes belonged to several functional categories, indicating high glucose had a profound effect on mesangial cell proliferation, protein synthesis, energy metabolism, and, somewhat unexpectedly, protein sorting and the cytoskeleton. Interestingly, several thiol antioxidative genes (glutathione peroxidase 1, peroxiredoxin 6, and thioredoxin 2) were found by microarray and confirmed by real-time PCR to be upregulated by high glucose. These changes suggested that the oxidative stress known to be induced in mesangial cells by high glucose might be buffered by upregulation of the thiol antioxidative pathway. Upregulation of thiol antioxidative genes also occurred in high-glucose-treated human mesangial cells and in glomeruli isolated from rats after 1 wk of streptozotocin-induced diabetes, but not in human proximal tubule cells. High glucose slightly increased lipid peroxidation and decreased the amount of reduced thiols in rat and human mesangial cells. Disruption of the thiol antioxidative pathway by two different thiol-oxidizing agents resulted in a three- to fivefold increase in high-glucose-induced lipid peroxidation. In summary, the present study provided a global view of the short-term effect of high glucose on mesangial cells at the level of mRNA expression and identified the upregulation of the thiol antioxidative pathway as an adaptational response of mesangial cells to high glucose.

Author List

Morrison J, Knoll K, Hessner MJ, Liang M

Author

Martin J. Hessner PhD Professor in the Pediatrics department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Adaptation, Physiological
Animals
Antioxidants
Cell Line
Gene Expression
Gene Expression Profiling
Glomerular Mesangium
Glucose
Humans
Lipid Peroxidation
Male
RNA, Messenger
Rats
Rats, Sprague-Dawley
Signal Transduction
Sulfhydryl Compounds
Up-Regulation