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The Inhibitory Effect of siRNAs on The High Glucose-Induced Overexpression of TGF- 1 in Mesangial Cells

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Affiliated Author(s)
이상숙강유나박관규김현철
Alternative Author(s)
Lee, Sang SookKang, Yu NaPark, Kwan KyuKim, Hyun Chul
Journal Title
Journal of Korean Medical Science
ISSN
1011-8934
Issued Date
2006
Keyword
Transforming Growth FactorsTransforming Growth Factor betaPlasminogen InactivatorsPlasminogen Activator Inhibitor 1Collagen Type IRNASmall Interfering
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-β1 was found to play an important role in the accumulation of ECM in the kidney. In this study, TGF-β1 RNA interference was used as an effective therapeutic strategy. The inhibitory effect of TGF-β1 small interfering RNAs (siRNAs) on the high glucose-induced overexpression of TGF-β1 in rat mesangial ceys (RMCs). A high levels of glucose induces TGF-β1 mRNA and protein, and TGF-β1 siRNAs reduce the ability of high glucose to stimulate their expression. We also examined the inhibitory effect of TGF-β1 siRNAs on the expression of plasminogen activator inhibitor (PAI)-1 and Collagen Type I which are down-regulators of TGF-β1. The expression of TGF-β1, PAI-1 and Collagen Type I was increased in RMCs that were stimulated by 30 mM glucose. TGF-β1 siRNAs reduces high glucose-induced TGF-β1, PAI-1, and Collagen Type I mRNA and protein expression in a dose-dependent manner. In conclusion, the present study demonstrates that TGF-β1 siRNAs effectively inhibits TGF-β1 mRNA and protein expression in RMCs. These suggest that TGF-β1 siRNAs through RNAi may be a useful tool for developing new therapeutic applications for the treatment of diabetic nephropathy.
Department
Dept. of Pathology (병리학)
Dept. of Internal Medicine (내과학)
Publisher
School of Medicine
Citation
Hey-Jeong Noh et al. (2006). The Inhibitory Effect of siRNAs on The High Glucose-Induced Overexpression of TGF- 1 in Mesangial Cells. Journal of Korean Medical Science, 21(3), 430–435. doi: 10.3346/jkms.2006.21.3.430
Type
Article
ISSN
1011-8934
DOI
10.3346/jkms.2006.21.3.430
URI
https://kumel.medlib.dsmc.or.kr/handle/2015.oak/33812
Appears in Collections:
1. School of Medicine (의과대학) > Dept. of Internal Medicine (내과학)
1. School of Medicine (의과대학) > Dept. of Pathology (병리학)
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