140 150

Cited 0 times in

Therapy with antisense TGF-beta1 oligodeoxynucleotides reduces kidney weight and matrix mRNAs in diabetic mice.

Authors
 DONG CHEOL HAN  ;  BRENDA B. HOFFMAN  ;  SOON WON HONG  ;  JIA GUO  ;  FUAD N. ZIYADEH 
Citation
 American Journal of Physiology - Renal Physiology, Vol.278(4) : F628-F634, 2000 
Journal Title
 American Journal of Physiology - Renal Physiology 
ISSN
 1931-857X 
Issue Date
2000
MeSH
Animals ; Cell Line, Transformed ; Diabetes Mellitus, Experimental/metabolism* ; Diabetes Mellitus, Experimental/pathology* ; Extracellular Matrix/genetics ; Hypertrophy ; Kidney/metabolism ; Kidney/pathology* ; Kidney Tubules, Proximal/cytology ; Kidney Tubules, Proximal/metabolism ; Mice ; Mice, Inbred C57BL ; Oligonucleotides, Antisense/pharmacology* ; Organ Size/drug effects ; RNA, Messenger/metabolism ; Reference Values ; Transforming Growth Factor beta/genetics* ; Transforming Growth Factor beta/metabolism
Keywords
transforming growth factor-b1 ; nephropathy ; proximal tubule ; glucose ; collagen type IV ; fibronectin ; osmotic minipumps
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- beta1 (TGF-beta1) expression may mediate diabetic renal hypertrophy, we investigated the effects of antisense TGF-beta1 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 microM) exhibited increased (3)[H]leucine incorporation by 120% and total TGF-beta1 protein by 50% vs. culture in 5.5 mM D-glucose. Antisense ODN significantly decreased the high-glucose-stimulated TGF-beta1 secretion and leucine incorporation. Continuous infusion for 10 days of ODN (100 microg/day) was achieved via osmotic minipumps in diabetic and nondiabetic mice. Sense ODN-treated streptozotocin-diabetic mice had 15.3% increase in kidney weight, 70% increase in alpha1(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-beta1 protein levels and attenuated the increase in kidney weight and the alpha1(IV) collagen and fibronectin mRNAs. In conclusion, therapy with antisense TGF-beta1 ODN decreases TGF-beta1 production 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.
Files in This Item:
T200002013.pdf Download
DOI
10.1152/ajprenal.2000.278.4.F628
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Pathology (병리학교실) > 1. Journal Papers
Yonsei Authors
Hong, Soon Won(홍순원) ORCID logo https://orcid.org/0000-0002-0324-2414
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/171616
사서에게 알리기
  feedback

qrcode

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

Browse

Links