| First Author | Fujimoto M | Year | 2003 |
| Journal | Biochem Biophys Res Commun | Volume | 305 |
| Issue | 4 | Pages | 1002-7 |
| PubMed ID | 12767930 | Mgi Jnum | J:113599 |
| Mgi Id | MGI:3687078 | Doi | 10.1016/s0006-291x(03)00885-4 |
| Citation | Fujimoto M, et al. (2003) Mice lacking Smad3 are protected against streptozotocin-induced diabetic glomerulopathy. Biochem Biophys Res Commun 305(4):1002-7 |
| abstractText | Transforming growth factor-beta (TGF-beta) has been implicated in the development of diabetic glomerulopathy. In order to evaluate a role of Smad3, one of the major signaling molecules downstream of TGF-beta, in the pathogenesis of diabetic glomerulopathy, Smad3-null mice were made diabetic with streptozotocin injection and analyzed 4 weeks after induction of diabetes. Electron microscopy revealed that the thickness of glomerular basement membrane (GBM) in wild-type diabetic mice was significantly higher than that in non-diabetic mice, whereas no appreciable GBM thickening was found in Smad3-null diabetic mice. Urinary albumin excretion was dramatically increased in wild-type diabetic mice, whereas Smad3-null diabetic mice did not show any overt albuminuria. Northern blotting revealed that mRNA levels of fibronectin and alpha 3 chain of type IV collagen (alpha 3Col4) in renal cortex of wild-type diabetic mice were approximately twice as much as those of non-diabetic mice, whereas their mRNA levels were not increased in Smad3-null diabetic mice. Real-time polymerase chain reaction (PCR) also confirmed diabetes-induced upregulation of fibronectin and alpha 3Col4 in glomeruli of wild-type mice. Glomerular expression of TGF-beta 1, as assessed by real-time PCR, was enhanced to a similar degree in wild-type and smad3-null diabetic mice, indicating that the observed differences between wild-type and Smad3-null mice are not attributable to difference in the expression of TGF-beta 1. These data clearly demonstrate a critical role of Smad3 in the early phase of diabetic glomerulopathy. This may be due at least partly to the present findings that diabetes-induced upregulation of fibronectin and alpha 3Col4 is dependent on Smad3 function. |
