title: Sp1-decoy oligodeoxynucleotide inhibits high glucose-induced mesangial cell proliferation.
abstract: 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.
authors.affiliation: Kidney Institute, Keimyung University School of Medicine, 194 Dongsan-Dong, Jung-Gu, Daegu 700-712, Republic of Korea.
authors.forename: Young-Mi
authors.initials: YM
authors.lastname: Chae
authors.forename: Kwan-Kyu
authors.initials: KK
authors.lastname: Park
authors.forename: Junji
authors.initials: J
authors.lastname: Magae
authors.forename: In-Seon
authors.initials: IS
authors.lastname: Lee
authors.forename: Cheorl-Ho
authors.initials: CH
authors.lastname: Kim
authors.forename: Hyun-Chul
authors.initials: HC
authors.lastname: Kim
authors.forename: SaHyun
authors.initials: S
authors.lastname: Hong
authors.forename: Jin-Gu
authors.initials: JG
authors.lastname: Lee
authors.forename: In-Jang
authors.initials: IJ
authors.lastname: Choi
authors.forename: Hyun-Soo
authors.initials: HS
authors.lastname: Kim
authors.forename: Kwan-Sik
authors.initials: KS
authors.lastname: Min
authors.forename: In-Kyu
authors.initials: IK
authors.lastname: Lee
authors.forename: Young-Chae
authors.initials: YC
authors.lastname: Chang
mesh_terms: 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*
chemical_list: D017931:DNA Primers; D009838:Oligodeoxyribonucleotides; D016329:Sp1 Transcription Factor; D005947:Glucose