| Authors |
Zhang H, Schin M, Saha J, Burke K, Holzman LB, Filipiak W, Saunders T, Xiang M,
Heilig CW, Brosius FC
|
| Submitted By |
Frank Brosius on 8/11/2010 |
| Status |
Published |
| Journal |
American journal of physiology. Renal physiology |
| Year |
2010 |
| Date Published |
7/1/2010 |
| Volume : Pages |
299 : F91 - F98 |
| PubMed Reference |
20375116 |
| Abstract |
Increased expression of the facilitative glucose transporter, GLUT1, leads to
glomerulopathy that resembles diabetic nephropathy, whereas prevention of
enhanced GLUT1 expression retards nephropathy. While many of the GLUT1-mediated
effects are likely due to mesangial cell effects, we hypothesized that increased
GLUT1 expression in podocytes also contributes to the progression of diabetic
nephropathy. Therefore, we generated two podocyte-specific GLUT1 transgenic
mouse lines (driven by a podocin promoter) on a db/m C57BLKS background. Progeny
of the two founders were used to generate diabetic db/db and control db/m
littermate mice. Immunoblots of glomerular lysates showed that transgenic mice
had a 3.5-fold (line 1) and 2.1-fold (line 2) increase in GLUT1 content compared
with wild-type mice. Both lines showed similar increases in fasting blood
glucose and body weights at 24 wk of age compared with wild-type mice. Mesangial
index (percent PAS-positive material in the mesangial tuft) increased 88% (line
1) and 75% (line 2) in the wild-type diabetic mice but only 48% (line 1) and 39%
(line 2) in the diabetic transgenic mice (P < 0.05, transgenic vs. wild-type
mice). This reduction in mesangial expansion was accompanied by a reduction in
fibronectin accumulation, and vascular endothelial growth factor (VEGF) levels
increased only half as much in the transgenic diabetic mice as in wild-type
diabetic mice. Levels of nephrin, neph1, CD2AP, podocin, and GLUT4 were not
significantly different in transgenic compared with wild-type mice. Taken
together, increased podocyte GLUT1 expression in diabetic mice does not
contribute to early diabetic nephropathy; surprisingly, it protects against
mesangial expansion and fibronectin accumulation possibly by blunting podocyte
VEGF increases.
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