Sp1-decoy oligodeoxynucleotide inhibits high glucose-induced mesangial cell proliferation.
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-beta1 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.
Chae
Young-Mi
YM
Kidney Institute, Keimyung University School of Medicine, 194 Dongsan-Dong, Jung-Gu, Daegu 700-712, Republic of Korea.
Park
Kwan-Kyu
KK
Magae
Junji
J
Lee
In-Seon
IS
Kim
Cheorl-Ho
CH
Kim
Hyun-Chul
HC
Hong
SaHyun
S
Lee
Jin-Gu
JG
Choi
In-Jang
IJ
Kim
Hyun-Soo
HS
Min
Kwan-Sik
KS
Lee
In-Kyu
IK
Chang
Young-Chae
YC
D000818:Animals; D001483:Base Sequence; D002455:Cell Division / Q000187:drug effects*; D017931:DNA Primers; D024202:Electrophoretic Mobility Shift Assay; D005920:Glomerular Mesangium / Q000166:cytology / Q000187:drug effects*; D005947:Glucose / Q000494:pharmacology*; D009838:Oligodeoxyribonucleotides / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D016329:Sp1 Transcription Factor / Q000235:genetics*
D017931:DNA Primers; D009838:Oligodeoxyribonucleotides; D016329:Sp1 Transcription Factor; D005947:Glucose