Theraphy with antisense TGF-β1 oligodeoxynucleotide reduces renal hypertrophy and matrix mRNAs in diabetic mice = TGF-베타1 ANTISENSE OLIGODEOXYUNCLEOTIDE가 쥐 혈관간세포 TGF-베타1과 제4형 COLLAGEN mRNA에 미치는 영향

다국어 초록 (Multilingual Abstract)

Inhibition of gene expression by antisense oligodeoxynucleotides (ODNs) relies on their ability to bind complementary mRNA sequences and prevent translation. The proximal tubule is a suitable target for ODN therapy in vivo because circulating ODNs accumulate in the proximal tubule in high concentrations. Since increased proximal tubular TGF-β1 expression may mediate diabetic renal hypertrophy, we investigated the effects of antisense TGF-β1 ODN on the high glucose-induced proximal tubular epithelial cell hypertrophy in tissue culture and on diabetic renal hypertrophy in vivo. Mouse proximal tubular cells grown in 25 mM D-glucose and exposed to sense ODN as control (1㎛) exhibited increased ³[H]-leucine incorporation by 120% and total TGF- β1 protein by 50% vs culture in 5.5 mM D-glucose. Antisense ODN significantly decreased the high glucose-stimulated TGF- β1 secretion and leucine incorporation. Continuous infusion for 10 days of ODN (100 ㎍/day) was achieved via osmotic mini-pumps in diabetic and nondiabetic mice. Sense ODN-treated streptozotocin-diabetic mice had 15.3% increase in kidney weight, 70% increase in α1(IV) collagen and 46% increase in fibronectin mRNA levels compared with nondiabetic mice. Treatment of diabetic mice with antisense ODN partially but significantly decreased kidney TGF- β1 protein levels and attenuated the increase in kidney weight and the α1(IV) collagen and fibronectin mRNAs. In conclusion, therapy with antisense TGF- β1 ODN decreases TGF- β1 production and attenuates high glucose-induced proximal tubular cell hypertrophy in vitro and partially prevents kidney hypertrophy and the increase in extracellular matrix expression in diabetic mice.

목차 (Table of Contents)

• Abstract
• 1. Introdution
• 2. Methods
• 3. Results
• 4. Discussion
• References