| First Author | Suzuki S | Year | 2007 |
| Journal | Am J Pathol | Volume | 171 |
| Issue | 2 | Pages | 473-83 |
| PubMed ID | 17620370 | Mgi Jnum | J:123921 |
| Mgi Id | MGI:3719966 | Doi | 10.2353/ajpath.2007.070279 |
| Citation | Suzuki S, et al. (2007) Renal damage in obstructive nephropathy is decreased in Skp2-deficient mice. Am J Pathol 171(2):473-83 |
| abstractText | Ubiquitin-dependent degradation of the cyclin-dependent kinase inhibitor p27 mediated by SCF-Skp2 ubiquitin ligase is involved in cell cycle regulation. Proliferation of tubular cells is a characteristic feature in obstructed kidneys of unilateral ureteral obstruction. Comparing Skp2(+/+) mice with Skp2(-/-) mice, we investigated the involvement of Skp2, a component of SCF-Skp2 ubiquitin ligase for p27, in the progression of renal lesions in unilateral ureteral obstructed kidneys. mRNA expression of Skp2 was markedly increased in the obstructed kidneys from Skp2(+/+) mice and peaked 3 days after unilateral ureteral obstruction. Renal atrophy, tubular dilatation, tubulointerstitial fibrosis, and increases in alpha-smooth muscle actin expression, the number of tubular cells, and proliferating tubular cells positive for Ki67 were observed in the obstructed kidneys from Skp2(+/+) mice; however, these findings were significantly attenuated in Skp2(-/-) mice. The p27 protein level was increased in the obstructed kidneys but was significantly greater in Skp2(-/-) mice. The number of Ki67-positive p27-negative cells was lower in obstructed kidneys from Skp2(-/-) mice than Skp2(+/+) mice, whereas that of Ki67-negative p27-positive cells was greater in Skp2(-/-) mice. These findings suggest that p27 accumulation, which results from SCF-Skp2 ubiquitin ligase deficiency in Skp2(-/-) mice, is involved in the amelioration of renal damage induced by obstructive nephropathy. |
