Abstract:
:Transcription factor Sp-1 is an important fibrogenic factor that is involved in the pathogenesis of diabetic nephropathy. In this study, we examined the effect of Sp1 decoy oligodeoxynucleotides (ODNs) on the extracellular matrix (ECM) gene expression in cultured rat mesangial cells (RMC) and streptozotocin (STZ)-induced diabetic rats. The ring-type Sp1 decoy ODNs significantly decreased ECM mRNA expression and Sp1 binding to the promoter region of these PDGF-induced genes in RMC. In addition, the decoy ODNs was introduced into the left renal artery of diabetic rat using the hemagglutinating virus of Japan (HVJ)-liposome mediated gene transfer method and effectively delivered to the kidney. On 14 days after ring-type Sp1 decoy ODNs injection, type IV collagen, fibronectin mRNA, and protein expression were markedly decreased, and the rate of urinary creatinine excretion was reduced in the ring-type Sp1 decoy ODNs-treated diabetic rats. These results indicated that the ring-type Sp1 decoy ODNs would be superior to P-Sp1 ODNs. Also, the R-Sp1 decoy ODN when introduced in vivo, effectively reduced ECM production during the progression of nephropathy. Therefore, ring-type Sp1 decoy is a promising tool for developing new therapeutic applications for progressive diabetic nephropathy.
journal_name
J Cell Biochemjournal_title
Journal of cellular biochemistryauthors
Kang JH,Chae YM,Park KK,Kim CH,Lee IS,Chang YCdoi
10.1002/jcb.21440subject
Has Abstractpub_date
2008-02-01 00:00:00pages
663-74issue
2eissn
0730-2312issn
1097-4644journal_volume
103pub_type
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