| First Author | Nath KA | Year | 2011 |
| Journal | Am J Physiol Renal Physiol | Volume | 301 |
| Issue | 2 | Pages | F436-42 |
| PubMed ID | 21525133 | Mgi Jnum | J:175290 |
| Mgi Id | MGI:5285070 | Doi | 10.1152/ajprenal.00162.2011 |
| Citation | Nath KA, et al. (2011) Genetic deficiency of Smad3 protects against murine ischemic acute kidney injury. Am J Physiol Renal Physiol 301(2):F436-42 |
| abstractText | TGF-beta1 contributes to chronic kidney disease, at least in part, via Smad3. TGF-beta1 is induced in the kidney following acute ischemia, and there is increasing evidence that TGF-beta1 may protect against acute kidney injury. As there is a paucity of information regarding the functional significance of Smad3 in acute kidney injury, the present study explored this issue in a murine model of ischemic acute kidney injury in Smad3(+/+) and Smad3(-/-) mice. We demonstrate that, at 24 h after ischemia, Smad3 is significantly induced in Smad3(+/+) mice, whereas Smad3(-/-) mice fail to express this protein in the kidney in either the sham or postischemic groups. Compared with Smad3(+/+) mice, and 24 h following ischemia, Smad3(-/-) mice exhibited greater preservation of renal function as measured by blood urea nitrogen (BUN) and serum creatinine; less histological injury assessed by both semiquantitative and qualitative analyses; markedly suppressed renal expression of IL-6 and endothelin-1 mRNA (but comparable expression of MCP-1, TNF-alpha, and heme oxygenase-1 mRNA); and no increase in plasma IL-6 levels, the latter increasing approximately sixfold in postischemic Smad3(+/+) mice. We conclude that genetic deficiency of Smad3 confers structural and functional protection against acute ischemic injury to the kidney. We speculate that these effects may be mediated through suppression of IL-6 production. Finally, we suggest that upregulation of Smad3 after an ischemic insult may contribute to the increased risk for chronic kidney disease that occurs after acute renal ischemia. |
