Cellular senescence in livers from children with end stage liver disease.
BACKGROUND
Senescent cells occur in adults with cirrhotic livers independent of the etiology.


OBJECTIVE
Investigate the presence rate of cellular senescence and expression of cell cycle check points in livers from children with end stage disease.


RESULTS
Livers of five children aged three years or less undergoing liver transplantation due to tyrosinemia (n = 1), biliary atresia (n = 2), or fulminant hepatitis (n = 2) were analyzed for senescence associated beta-galactosidase (SA-betagal) activity and p16INK4a, p21cip1 and p53. All livers displayed positive cellular staining for SA-betagal in the canals of Hering and interlobular biliary ducts. In the presence of cirrhosis (3/5 cases) SA-betagal was found at the cholangioles and hepatocytes surrounding the regenerative nodules. Children with fulminant hepatic failure without cirrhosis had significant ductular transformation with intense SA-betagal activity. No SA-betagal activity was evident in the fibrous septa. Staining for p53 had a similar distribution to that observed for SA-betagal. Staining for p16(INK4a) and p21(cip1) was positive in the explanted liver of the patient with tyrosinemia, in the hepatocytes, the canals of Hering, cholangioles and interlobular bile ducts. In the livers with fulminant hepatitis, p21(cip1) staining occurred in the areas of ductular transformation and in the interlobular bile ducts.


CONCLUSIONS
Cellular senescence in livers of children with end stage disease is associated with damage rather than corresponding to an age dependent phenomenon. Further studies are needed to support the hypothesis that these senescence markers correlate with disease progression.
Gutierrez-Reyes
Gabriela
G
Department of Experimental Medicine, School of Medicine, Universidad Nacional Autónoma de México, (UNAM), Hospital General de México, [corrected] Mexico City, Mexico.
del Carmen Garcia de Leon
Maria
M
Varela-Fascinetto
Gustavo
G
Valencia
Pedro
P
Pérez Tamayo
Ruy
R
Rosado
Claudia Gonzalez
CG
Labonne
Blanca Farfan
BF
Rochilin
Norma Morales
NM
Garcia
Rosalinda Martinez
RM
Valadez
Jonathan Aguirre
JA
Latour
Gabriela Togno
GT
Corona
Dana Lau
DL
Diaz
Guillermo Robles
GR
Zlotnik
Albert
A
Kershenobich
David
D
D001656:Biliary Atresia; D016922:Cellular Senescence; D002648:Child; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000032:analysis; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000032:analysis; D006801:Humans; D008099:Liver / Q000473:pathology; D008103:Liver Cirrhosis / Q000209:etiology / Q000473:pathology; D017093:Liver Failure / Q000209:etiology* / Q000473:pathology*; D017114:Liver Failure, Acute; D016031:Liver Transplantation; D016159:Tumor Suppressor Protein p53 / Q000032:analysis; D020176:Tyrosinemias
C493956:CDKN1A protein, human; D019941:Cyclin-Dependent Kinase Inhibitor p16; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016159:Tumor Suppressor Protein p53