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Titolo:
Therapy with antisense TGF-beta 1 oligodeoxynucleotides reduces kidney weight and matrix mRNAs in diabetic mice
Autore:
Han, DC; Hoffman, BB; Hong, SW; Guo, J; Ziyadeh, FN;
Indirizzi:
Univ Penn, Sch Med, Renal Electrolyte & Hypertens Div, Philadelphia, PA 19104 USA Univ Penn Philadelphia PA USA 19104 rtens Div, Philadelphia, PA 19104 USA Univ Penn, Sch Med, Dept Med, Penn Ctr Mol Studies Kidney Dis, Philadelphia, PA 19104 USA Univ Penn Philadelphia PA USA 19104 idney Dis, Philadelphia, PA 19104 USA
Titolo Testata:
AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY
fascicolo: 4, volume: 278, anno: 2000,
pagine: F628 - F634
SICI:
0363-6127(200004)278:4<F628:TWAT1O>2.0.ZU;2-Q
Fonte:
ISI
Lingua:
ENG
Soggetto:
PROXIMAL TUBULAR CELLS; GROWTH-FACTOR-BETA; HIGH GLUCOSE; RENAL HYPERTROPHY; GENE-EXPRESSION; ANGIOTENSIN-II; TRANSFORMING GROWTH-FACTOR-BETA-1; ELEVATED GLUCOSE; TGF-BETA; OLIGONUCLEOTIDES;
Keywords:
transforming growth factor-beta 1; nephropathy; proximal tubule; glucose; collagen type IV; fibronectin; osmotic mini-pumps;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
34
Recensione:
Indirizzi per estratti:
Indirizzo: Ziyadeh, FN Univ Penn, Sch Med, Renal Electrolyte & Hypertens Div, 700 Clin Res Bldg,415 Curie Blvd, Philadelphia, PA 19104 USA Univ Penn 700 Clin Res Bldg,415 Curie Blvd Philadelphia PA USA 19104
Citazione:
D.C. Han et al., "Therapy with antisense TGF-beta 1 oligodeoxynucleotides reduces kidney weight and matrix mRNAs in diabetic mice", AM J P-REN, 278(4), 2000, pp. F628-F634

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. Because increased proximal tubular transforming growth factor-beta 1(TGF-beta 1) expression may mediate diabetic renal hypertrophy, we investigated the effects of antisense TGF-beta 1 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 mu M) exhibited increased (3)[H]leucine incorporation by 120% and total TGF-beta 1 protein by 50% vs. culture in 5.5 mM D-glucose. Antisense ODN significantly decreased the high-glucose-stimulated TGF-beta 1 secretion and leucine incorporation. Continuous infusion for 10 days of ODN (100 mu g/day) was achieved via osmotic minipumps in diabetic and nondiabetic mice. Sense ODN-treated streptozatacin-diabetic mice had 15.3% increase in kidney weight, 70% increase in alpha 1(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-beta 1 protein levels and attenuated the increase in kidney weight and the alpha 1(IV) collagen and fibronectin mRNAs. In conclusion, therapy with antisense TGF-beta 1 ODN decreases TGF-beta 1production and attenuates high-glucose-induced proximal tubular cell hypertrophy in vitro and partially prevents the increase in kidney weight and extracellular matrix expression in diabetic mice.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 07/08/20 alle ore 07:03:12