title: P53-Rb signaling pathway is involved in tubular cell senescence in renal ischemia/reperfusion injury.
abstract: OBJECTIVE
  To investigate the course of tubular cell senescence and expressions of p53, p21, and Rb during the late phase of ischemia/reperfusion (IRI) in the kidney, and assess the effects of the p53-Rb pathway on tubular cell senescence.
  
  
  METHODS
  Experimental models of unilateral renal IRI were used in p53 (+/+) and p53 (-/-) mice. Histological changes at the tubular level, progress of cell senescence, and the expression of Rb, p21, and/or p53 proteins in tubular cells were studied at different moments in time after IRI.
  
  
  RESULTS
  Chronic tubulointerstitial fibrosis was much more severe and widely distributed in IRI kidneys of p53 (+/+) mice in later stages than in earlier stages. Senescent tubular cells were significantly increased at 3 and 6 months after IRI. In contrast, in contralateral kidneys of p53 (+/+) mice and in both kidneys of p53 (-/-) mice, almost no senescent cells were observed at 1 and 3 months after IRI, and only a few senescent cells were detected in IRI kidneys of p53 (-/-) mice at 6 months. In mice of both genotypes, cell senescence was correlated with the expression levels of p53, p21, and Rb proteins.
  
  
  CONCLUSIONS
  The IRI accelerated tubular cell senescence is presumed to be one of the mechanisms of the "long-term effect" of IRI. Furthermore, the activation of p53-Rb signaling pathway may play a vital role in tubular cell senescence induced by IRI.
authors: Center of Medical Molecular Genetics, State Key Laboratory of Trauma, Burn and Combined Injury, Daping Hospital, Third Military Medical University, Chongqing 400042, China. likailong1966@163.com
authors: Li
authors: L
authors: Kailong
authors: Xiaolan
authors: X
authors: Du
authors: He
authors: H
authors: Yani
authors: Zhao
authors: Z
authors: Lin
authors: Yang
authors: Y
authors: Jvrong
authors: Song
authors: S
authors: Ruihua
authors: Chen
authors: C
authors: Lin
mesh_terms: D000818:Animals; D016922:Cellular Senescence; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism; D016158:Genes, p53 / Q000502:physiology*; D007674:Kidney Diseases / Q000235:genetics* / Q000473:pathology; D007684:Kidney Tubules / Q000378:metabolism / Q000473:pathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D015427:Reperfusion Injury / Q000235:genetics* / Q000473:pathology; D016160:Retinoblastoma Protein / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D001616:beta-Galactosidase / Q000378:metabolism
chemical_list: D050759:Cyclin-Dependent Kinase Inhibitor p21; D016160:Retinoblastoma Protein; D016159:Tumor Suppressor Protein p53; D001616:beta-Galactosidase