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p53-Rb signaling pathway is involved in tubular cell senescence in renal ischemia/reperfusion injury

LI KAILONG1,2, DU XIAOLAN1, HE YANI2, ZHAO LIN1, YANG JVRONG2, SONG RUIHUA1, CHEN LIN1

1 Center of Medical Molecular Genetics, State Key Laboratory of Trauma, Burn and Combined Injury;
2 Department of Nephrology, Daping Hospital, Third Military Medical University, Chongqing 400042, China.
Address correspondence to: Dr. Li kailong. Department of Nephrology, Daping Hospital, 10 Changjiang Zhi Road Daping, Chongqing 400042, CHINA. Fax: +86-23-68710162. E-mail: likailong1966@163.com

BIOCELL 2007, 31(2), 213-223. https://doi.org/10.32604/biocell.2007.31.213

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. Conclusion: 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.

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KAILONG, L., XIAOLAN, D., YANI, H., LIN, Z., JVRONG, Y. et al. (2007). p53-Rb signaling pathway is involved in tubular cell senescence in renal ischemia/reperfusion injury. BIOCELL, 31(2), 213–223.

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