The Inhibitory Effect of siRNAs on The High Glucose-Induced Overexpression of TGF-beta1 in Mesangial Cells.
10.3346/jkms.2006.21.3.430
- Author:
Hey Jeong NOH
1
;
Hyun Chul KIM
;
Sang Sook LEE
;
Yu Na KANG
;
Young Mi CHAE
;
Kwan Kyu PARK
Author Information
1. Department of Pathology, Keimyung University School of Medicine, Daegu, Korea.
- Publication Type:Original Article ; Research Support, Non-U.S. Gov't
- Keywords:
Transforming Growth Factors;
Transforming Growth Factor beta;
Plasminogen Inactivators;
Plasminogen Activator Inhibitor 1;
Collagen Type I;
RNA, Small Interfering
- MeSH:
Transforming Growth Factor beta1/*metabolism;
Rats, Sprague-Dawley;
Rats;
RNA, Small Interfering/*metabolism;
Microscopy, Fluorescence;
Mesangial Cells/*metabolism;
Male;
Glucose/*metabolism;
Glomerular Mesangium/*metabolism;
Gene Expression Regulation;
Diabetic Nephropathies/pathology;
Collagen Type I/metabolism;
Cells, Cultured;
Cell Proliferation;
Animals
- From:Journal of Korean Medical Science
2006;21(3):430-435
- CountryRepublic of Korea
- Language:English
-
Abstract:
Diabetic nephropathy is characterized by an expansion of the glomerular mesangium, caused by mesangial cell proliferation and an excessive accumulation of extracellar matrix (ECM) proteins, which eventually leading to glomerulosclerosis. TGF-beta1 was found to play an important role in the accumulation of ECM in the kidney. In this study, TGF-beta1 RNA interference was used as an effective therapeutic strategy. The inhibitory effect of TGF-beta1 small interfering RNAs (siRNAs) on the high glucose-induced overexpression of TGF-beta1 in rat mesangial ceys (RMCs). A high levels of glucose induces TGF-beta1 mRNA and protein, and TGF-beta1 siRNAs reduce the ability of high glucose to stimulate their expression. We also examined the inhibitory effect of TGF-beta1 siRNAs on the expression of plasminogen activator inhibitor (PAI)-1 and Collagen Type I which are down-regulators of TGF-beta1. The expression of TGF-beta1, PAI-1 and Collagen Type I was increased in RMCs that were stimulated by 30 mM glucose. TGF-beta1 siRNAs reduces high glucose-induced TGF-beta1, PAI-1, and Collagen Type I mRNA and protein expression in a dose-dependent manner. In conclusion, the present study demonstrates that TGF-beta1 siRNAs effectively inhibits TGF-beta1 mRNA and protein expression in RMCs. These suggest that TGF-beta1 siRNAs through RNAi may be a useful tool for developing new therapeutic applications for the treatment of diabetic nephropathy.
