Antisense GLUT-1 protects mesangial cells from glucose induction of GLUT-1and fibronectin expression

Citation
Cw. Heilig et al., Antisense GLUT-1 protects mesangial cells from glucose induction of GLUT-1and fibronectin expression, AM J P-REN, 280(4), 2001, pp. F657-F666
Citations number
36
Language
INGLESE
art.tipo
Article
Categorie Soggetti
da verificare
Journal title
AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY
ISSN journal
0363-6127 → ACNP
Volume
280
Issue
4
Year of publication
2001
Pages
F657 - F666
Database
ISI
SICI code
0363-6127(200104)280:4<F657:AGPMCF>2.0.ZU;2-G
Abstract
A stable clone of rat mesangial cells expressing antisense GLUT-1 (i.e., MC GT1AS cells) was developed to protect them from high glucose exposure. GLUT -1 protein was reduced 50%, and the 2-deoxy-[H-3] glucose uptake rate was r educed 33% in MCGT1AS. MCLacZ control cells and MCGT1 GLUT-1-overexpressing cells were used for comparisons. In MCLacZ, 20 mM D-glucose increased GLUT -1 transcription 90% vs. no increase in MCGT1AS. Glucose (8 mM) and 12 mM x ylitol [a hexose monophosphate (HMP) shunt substrate] did not stimulate GLU T-1 transcription. An 87% replacement of the standard 8 mM D-glucose with 3 -O-methylglucose reduced GLUT-1 transcription 80%. D-Glucose (20 mM) increa sed fibronectin mRNA and protein by 47 and 100%, respectively, in MCLacZ vs . no increases in MCGT1AS. Fibronectin synthesis was elevated 48% in MCGT1 and reduced 44% in MCGT1AS. We conclude that 1) transcription of GLUT-1 in response to D-glucose depends on glucose metabolism, although not through t he HMP shunt, and 2) antisense GLUT-1 treatment of mesangial cells blocks D -glucose-induced GLUT-1 and fibronectin expression, thereby demonstrating a protective effect that could be beneficial in the setting of diabetes.