TY - JOUR
T1 - Renal damage in obstructive nephropathy is decreased in Skp2-deficient mice
AU - Suzuki, Sayuri
AU - Fukasawa, Hirotaka
AU - Kitagawa, Kyoko
AU - Uchida, Chiharu
AU - Hattori, Takayuki
AU - Isobe, Tomoyasu
AU - Oda, Toshiaki
AU - Misaki, Taro
AU - Ohashi, Naro
AU - Nakayama, Keiko
AU - Nakayama, Keiichi I.
AU - Hishida, Akira
AU - Yamamoto, Tatsuo
AU - Kitagawa, Masatoshi
N1 - Copyright:
Copyright 2017 Elsevier B.V., All rights reserved.
PY - 2007/8
Y1 - 2007/8
N2 - 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 α-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.
AB - 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 α-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.
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U2 - 10.2353/ajpath.2007.070279
DO - 10.2353/ajpath.2007.070279
M3 - Article
C2 - 17620370
AN - SCOPUS:34548363730
VL - 171
SP - 473
EP - 483
JO - American Journal of Pathology
JF - American Journal of Pathology
SN - 0002-9440
IS - 2
ER -