Effect of Antisense TGF-beta1 Oligodeoxynucleotides in Streptozotocin-Induced Diabetic Rat Kidney.
10.3346/jkms.2004.19.3.374
- Author:
Hyo Soon JEONG
1
;
Kwan Kyu PARK
;
Sang Pyo KIM
;
In Jang CHOI
;
In Kyu LEE
;
Hyun Chul KIM
Author Information
1. Department of Anatomy, Keimyung University School of Medicine, Daegu, Korea.
- Publication Type:Original Article ; Research Support, Non-U.S. Gov't
- Keywords:
Transforming Growth Factors;
Diabetes Mellitus;
Oligonucleotides;
Streptozotocin
- MeSH:
Animals;
Blood Glucose/metabolism;
Cells, Cultured;
Diabetes Mellitus, Experimental/*therapy;
Enzyme-Linked Immunosorbent Assay;
Gene Transfer Techniques;
Immunohistochemistry;
Liposomes/chemistry;
Male;
Microscopy, Confocal;
Oligonucleotides, Antisense/metabolism/pharmacology/*therapeutic use;
RNA/metabolism;
RNA, Messenger/metabolism;
Rats;
Rats, Sprague-Dawley;
Reverse Transcriptase Polymerase Chain Reaction;
Streptozocin;
Support, Non-U.S. Gov't;
Time Factors;
Transfection;
Transforming Growth Factor beta/*genetics
- From:Journal of Korean Medical Science
2004;19(3):374-383
- CountryRepublic of Korea
- Language:English
-
Abstract:
Transforming growth factor (TGF)-beta1 is an important fibrogenic factor that is involved in the pathogenesis of diabetic nephropathy. We evaluated the effect of circular antisense TGF-beta1 oligodeoxynucleotides (ODNs) on the TGF-beta1 expression in the rat mesangial cell culture and in streptozotocin (STZ)-induced diabetic rats. Circular antisense TGF-beta1 ODNs were found to be stable in rat serum, significantly decreasing TGF-beta1 mRNA expression compared with linear antisense ODNs in the rat mesangial cell culture. Circular antisense TGF-beta1 ODNs were introduced into the tail vein of normal rats using hemagglutinating virus of Japan (HVJ)-liposome-mediated gene transfer method and were confirmed to be delivered effectively into the kidney, liver, lungs, and spleen. To inhibit the overexpression of TGF-beta1 in diabetic kidneys, we introduced circular antisense TGF-beta1 ODNs into the STZ-induced diabetic rats. On day 13 after circular antisense TGF-beta1 ODNs injection, TGF-beta1 mRNA and protein expression markedly decreased and urinary TGF-beta1 excretion rate also dropped in the circular antisense TGF-beta1 ODNs-treated diabetic rats. These results suggest that circular antisense TGF-beta1 ODNs may be a useful tool for developing new therapeutic application for progressive diabetic nephropathy.
