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Increased expression of p16(INK4a) and p27(Kip1) cyclin-dependent kinase inhibitor genes in aging human kidney and chronic allograft nephropathy.
Chkhotua, Archil B; Gabusi, Elena; Altimari, Annalisa; D'Errico, Antonia; Yakubovich, Michaela; Vienken, Joerg; Stefoni, Sergio; Chieco, Pasquale; Yussim, Alexander; Grigioni, Walter F.
Afiliación
  • Chkhotua AB; National Centre of Urology and Nephrology, Tbilisi, Georgia. achkhotua@hotmail.com
Am J Kidney Dis ; 41(6): 1303-13, 2003 Jun.
Article en En | MEDLINE | ID: mdl-12776284
BACKGROUND: The goal of the current study was to examine the potential value of p16(INK4a) and p27(Kip1) cyclin-dependent kinase inhibitor (CDKI) genes in the process of human kidney aging in vivo, and in the development of chronic allograft nephropathy (CAN). METHODS: Expression of p16(INK4a) and p27(Kip1) CDKI genes was evaluated and compared in 20 normal human kidney tissues of different ages (range, 21 to 80 years) and in 9 chronically rejected kidney grafts. Age dependency of marker expression was analyzed by the Pearson correlation and linear regression. RESULTS: Expression of p16 in cortical tubular (CTS) and interstitial (CIS) cells of normal kidney was age dependent (correlation coefficients: 0.608 and 0.726, 95% confidence interval [CI]: 0.227 to 0.828 and 0.417 to 0.884, respectively). Cortical tubular expression of p27 was also correlated with increasing age (0.672, 95% CI: 0.327 to 0.859). Linear regression analyses confirmed the linearity of marker relationship with age (coefficient of determination R(2):0.370, 0.452, and 0.527 for CIS p16, CTS p27, and CTS p16, respectively). The mean chronological and predicted graft ages (53 +/- 21 and 76 +/- 8.9 years, respectively) were significantly different (P = 0.0126). The glomeruli, tubules, and interstitial cells of rejected grafts expressed significantly higher levels of p16 and p27 than normal kidneys. Expression of p16 in glomerular and cortical interstitial cells was higher in grade 3 of CAN than in grade 2 (P = 0.013 and 0.004, respectively). CONCLUSION: The results of the current study show that expression of p16(INK4a) and p27(Kip1) CDKI genes is increased in cortical cells of the aging human kidney and in chronic allograft rejection, supporting the senescence theory of CAN.
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Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Envejecimiento / Regulación de la Expresión Génica / Trasplante de Riñón / Proteínas de Ciclo Celular / Genes p16 / Inhibidor p16 de la Quinasa Dependiente de Ciclina / Proteínas Supresoras de Tumor / Rechazo de Injerto / Enfermedades Renales Tipo de estudio: Etiology_studies Límite: Adolescent / Adult / Aged / Aged80 / Female / Humans / Male / Middle aged Idioma: En Revista: Am J Kidney Dis Año: 2003 Tipo del documento: Article País de afiliación: Georgia Pais de publicación: Estados Unidos
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Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Envejecimiento / Regulación de la Expresión Génica / Trasplante de Riñón / Proteínas de Ciclo Celular / Genes p16 / Inhibidor p16 de la Quinasa Dependiente de Ciclina / Proteínas Supresoras de Tumor / Rechazo de Injerto / Enfermedades Renales Tipo de estudio: Etiology_studies Límite: Adolescent / Adult / Aged / Aged80 / Female / Humans / Male / Middle aged Idioma: En Revista: Am J Kidney Dis Año: 2003 Tipo del documento: Article País de afiliación: Georgia Pais de publicación: Estados Unidos