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J Am Soc Nephrol 14:S279-S283, 2003
© 2003 American Society of Nephrology

Supplement Article

Transcriptome Profiling and the Pathogenesis of Diabetic Complications

Susan B. Connolly, Denise Sadlier, Niamh E. Kieran, Peter Doran and Hugh R. Brady

Department of Medicine and Therapeutics, Mater Misericordiae University Hospital, Conway Institute of Biomolecular and Biomedical Research, University College Dublin, and the Dublin Molecular Medicine Centre, Dublin, Ireland.

Correspondence to Dr. Peter Doran, Department of Medicine and Therapeutics, Mater Misericordiae University Hospital, University College Dublin, 44 Eccles Street, Dublin 7, Ireland. Phone: 353-1-7166319; Fax: 353-1-7166334;

ABSTRACT. Diabetes is an escalating problem worldwide and a major cause of vascular disease, renal failure, and blindness, among other complications. The cellular mediators of high glucose–induced injury include activation of protein kinase C, accumulation of cell sorbitol from increased flux through the aldose reductase pathway, and generation of advanced glycosylation end products and reactive oxygen species, among others. Current strategies for preventing and slowing the progression of the macrovascular and microvascular complications of diabetes include optimization of glycemic control and BP, angiotensin-converting enzyme inhibitors and angiotensin II blockers, and HMG CoA reductase inhibitors. However, there is an urgent need to develop new therapeutic strategies, as these interventions, although they may slow, rarely halt the progression of diabetic complications. Central to this process is the elucidation of the molecular events that drive this complex disease and that are potential therapeutic targets. This review discusses the promise offered in this regard by global monitoring of cellular or tissue mRNA expression (so-called transcriptomics) and illustrates the potential of this approach by focusing on recent studies on the pathogenesis of diabetic nephropathy. E-mail: deptofmedicine@mater.ie




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