GLUT-1 overexpression: Link between hemodynamic and metabolic factors in glomerular injury?

Luigi Gnudi, Gian Carlo Viberti, Leopoldo Raij, Veronica Rodriguez, Davina Burt, Pedro Cortes, Barry Hartley, Stephen Thomas, Sabrina Maestrini, Gabriella Gruden

Research output: Contribution to journalArticle

70 Scopus citations

Abstract

Mesangial matrix deposition is the hallmark of hypertensive and diabetic glomerulopathy. At similar levels of systemic hypertension, Dahl salt-sensitive but not spontaneously hypertensive rats (SHR) develop glomerular hypertension, which is accompanied by upregulation of transforming growth factor β1 (TGF-β1), mesangial matrix expansion, and sclerosis. GLUT-1 is ubiquitously expressed and is the predominant glucose transporter in mesangial cells. In mesangial cells in vitro, GLUT-1 overexpression increases basal glucose transport, resulting in excess fibronectin and collagen production. TGF-β1 has been shown to upregulate GLUT-1 expression. We demonstrated that in hypertensive Dahl salt-sensitive (S) rats fed 4% NaCl (systolic blood pressure [SBP]: 236±9 mm Hg), but not in similarly hypertensive SHR (SBP: 230±10 mm Hg) or their normotensive counterparts (Dahl S fed 0.5% NaCl, SBP: 145±5 mm Hg; and Wistar-Kyoto, SBP: 137±3 mm Hg), there was an 80% upregulation of glomerular GLUT-1 protein expression (P≤0.03). This was accompanied by a 2.7-fold upregulation of TGF-β1 protein expression in glomeruli of DSH compared with DSN rats (P=0.02). TGF-β1 expression was not upregulated and did not differ in the glomeruli of Wistar-Kyoto and SHR rats. As an in vitro surrogate of the in vivo hemodynamic stress imposed by glomerular hypertension, we used mechanical stretching of human and rat mesangial cells. We found that after 33 hours of stretching, mesangial cells overexpressed GLUT-1 (40%) and showed an increase in basal glucose transport of similar magnitude (both P≤0.01), which could be blocked with an anti TGF-β1-neutralizing antibody. These studies suggest a novel link between hemodynamic and metabolic factors that may cooperate in inducing progressive glomerular injury in conditions characterized by glomerular hypertension.

Original languageEnglish (US)
Pages (from-to)19-24
Number of pages6
JournalHypertension
Volume42
Issue number1
DOIs
StatePublished - Jul 1 2003

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Keywords

  • Experimental
  • Hypertension
  • Mesangium
  • Stress
  • Transforming growth factors

ASJC Scopus subject areas

  • Internal Medicine

Cite this

Gnudi, L., Viberti, G. C., Raij, L., Rodriguez, V., Burt, D., Cortes, P., Hartley, B., Thomas, S., Maestrini, S., & Gruden, G. (2003). GLUT-1 overexpression: Link between hemodynamic and metabolic factors in glomerular injury? Hypertension, 42(1), 19-24. https://doi.org/10.1161/01.HYP.0000075949.19968.EF