NDT Advance Access originally published online on January 31, 2006
Nephrology Dialysis Transplantation 2006 21(6):1514-1524; doi:10.1093/ndt/gfk089
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
© The Author [2006]. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org
Original Articles: Experimental Nephrology
Role of TGF-ß/GLUT1 axis in susceptibility vs resistance to diabetic glomerulopathy in the Milan rat model
1 Department of Clinical Sciences, ‘La Sapienza’ University, Rome, 2 Department of Cell Biology and Neurosciences, Istituto Superiore di Sanità, Rome and 3 Laboratory of Renal Immunopathology, San Carlo Borromeo Hospital, Milan, Italy
Correspondence and offprint requests to: Giuseppe Pugliese, MD, PhD, Dipartimento di Scienze Cliniche (Endocrinologia), Viale del Policlinico, 155 - 00161 Rome, Italy. Email: giuseppe.pugliese{at}uniroma1.it
Background. GLUT1 upregulation and increased glucose transport activity may contribute to extracellullar matrix (ECM) accumulation characterizing diabetic nephropathy (DN). Rats of the Milan hypertensive strain (MHS) are resistant to both hypertensive and diabetic renal disease, due to a haemodynamic protection. On the contrary, those of the Milan normotensive strain (MNS) develop spontaneous glomerulosclerosis, and when rendered diabetic, show typical morphological and haemodynamic changes.
Methods. To assess whether susceptibility to diabetic glomerulopathy in MNS rats is associated with higher glucose transporter 1 (GLUT1) expression (and glucose transport activity) vs MHS rats, diabetic and nondiabetic MNS and MHS rats were followed for 6 months and mesangial cells derived from these animals were exposed to high glucose (HG) vs normal glucose (NG) conditions.
Results. Glomerular expression of GLUT1 protein and ECM and transforming growth factor-ß (TGF-ß) mRNA was significantly upregulated in diabetic vs nondiabetic MNS, but not MHS rats. Upon exposure to HG and/or TGF-ß, mesangial cells from 1- and 8-month-old MNS rats showed higher glucose transport activity and GLUT1 membrane expression than those from age-matched MHS rats. Likewise, ECM and TGF-ß production increased more markedly in response to HG and/or TGF-ß in MNS vs MHS mesangial cells.
Conclusions. These data indicate that susceptibility to diabetic glomerulopathy in MNS rats is associated with increased GLUT1-dependent glucose transport activity in response to hyperglycaemia and/or TGF-ß, which may amplify ECM overproduction. Conversely, the haemodynamic protection from glomerulosclerosis in MHS rats is associated with lack of upregulation of TGF-ß/GLUT1 axis, thus supporting the concept that this axis may represent the link between haemodynamic and metabolic mechanisms of injury.
Keywords: diabetic nephropathy; extracellular matrix; glucose transport; GLUT1; renal haemodynamics; TGF-ß
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  Z. T. Bloomgarden Diabetic Nephropathy Diabetes Care, April 1, 2008; 31(4): 823 - 827. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Gnudi, S. M. Thomas, and G. Viberti Mechanical Forces in Diabetic Kidney Disease: A Trigger for Impaired Glucose Metabolism J. Am. Soc. Nephrol., August 1, 2007; 18(8): 2226 - 2232. [Abstract] [Full Text] [PDF]
|
|