Renal type I inositol 1,4,5-trisphosphate receptor is reduced in streptozotocin-induced diabetic rats and mice.
The mechanisms underlying glomerular hypertrophy and hyperfiltration in diabetes remain unclear. We have previously demonstrated that the cytokine transforming growth factor-beta1 (TGF-beta1) is increased in early diabetic kidney disease and TGF-beta1 inhibits the expression of the inositol 1,4,5-trisphosphate (IP3)-gated calcium channel, the type I IP3 receptor (IP3R), in mesangial cells. To test the hypothesis that reduced type I IP3R may be important in diabetic kidney disease, we evaluated type I IP3R expression in the kidney of streptozotocin-induced diabetic rats and mice. Two-week-old diabetic rats have decreased renal type I IP3R protein and mRNA levels. Immunostaining of normal rat kidney demonstrated presence of type I IP3R in glomerular and vascular smooth muscle cells, whereas diabetic rats had reduced staining in both compartments. Reduction of type I IP3R also occurred in parallel with renal hypertrophy, increased creatinine clearance, and increased renal TGF-beta1 expression in the diabetic rats. Two-week-old diabetic mice also had reduced renal type I IP3R protein and mRNA expression in association with renal hypertrophy and increased TGF-beta1 mRNA expression. These findings demonstrate that there is reduced type I IP3R in glomerular and vascular smooth muscle cells in the diabetic kidney, which may contribute to the altered renal vasoregulation and renal hypertrophy of diabetes.
Sharma
K
K
Nephrology Division, Pathology, and Cell Biology, Thomas Jefferson University School of Medicine, Philadelphia, Pennsylvania 19107, USA.
Wang
L
L
Zhu
Y
Y
DeGuzman
A
A
Cao
G Y
GY
Lynn
R B
RB
Joseph
S K
SK
D000818:Animals; D015152:Blotting, Northern; D015220:Calcium Channels / Q000378:metabolism*; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism* / Q000473:pathology; D053496:Inositol 1,4,5-Trisphosphate Receptors; D007668:Kidney / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D051381:Rats; D017207:Rats, Sprague-Dawley; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism*; D012016:Reference Values; D014018:Tissue Distribution; D016212:Transforming Growth Factor beta / Q000378:metabolism
D015220:Calcium Channels; D053496:Inositol 1,4,5-Trisphosphate Receptors; D018160:Receptors, Cytoplasmic and Nuclear; D016212:Transforming Growth Factor beta