Dept. of Pathology (병리학); Dept. of Internal Medicine (내과학); Dept. of Anatomy (해부학); Kidney Institute (신장연구소)
Biochemical and Biophysical Research Communications, Vol.319(2) : 550-555, 2004
Mesangial expansion caused by cell proliferation and glomerular extracellular matrix accumulation is one of the earliest renal abnormalities observed at the onset of hyperglycemia in diabetes mellitus. Transcription factor Sp1 is implicated in the transcriptional regulation of a wide range of genes participating in cell proliferation, and is assumed to play an essential role in mesangial expansion. We have generated a phosphorothioated double-stranded Sp1-decoy oligodeoxynucleotide that effectively blocks Sp1 binding to the promoter region for transcriptional regulation of transforming growth factor-β1 and plasminogen activator inhibitor-1. The Sp1-decoy oligodeoxynucleotide suppressed transcription of these cytokines and proliferation of primary rat mesangial cells in response to high glucose. These results suggest that the Sp1-decoy oligodeoxynucleotide could be a powerful tool in preventing the pathogenesis of renal hypertrophy.
Mesangial cell proliferation;
Transforming growth factor-β1;
Plasminogen activator inhibitor-1