Transcriptome profiling and the pathogenesis of diabetic complications.
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.
Connolly
Susan B
SB
Department of Medicine and Therapeutics, Mater Misericordiae University Hospital, Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Ireland.
Sadlier
Denise
D
Kieran
Niamh E
NE
Doran
Peter
P
Brady
Hugh R
HR
D000199:Actins / Q000378:metabolism; D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism; D055513:Connective Tissue Growth Factor; D048909:Diabetes Complications; D003920:Diabetes Mellitus / Q000235:genetics* / Q000378:metabolism; D020869:Gene Expression Profiling / Q000379:methods; D006801:Humans; D017874:Immediate-Early Proteins / Q000378:metabolism; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D011506:Proteins / Q000378:metabolism; D014158:Transcription, Genetic
D000199:Actins; C526317:CCN2 protein, human; D002352:Carrier Proteins; C486399:GREM1 protein, human; D017874:Immediate-Early Proteins; D036341:Intercellular Signaling Peptides and Proteins; D011506:Proteins; D055513:Connective Tissue Growth Factor