Cellular senescence in livers from children with end stage liver disease

Gabriela Gutierrez-Reyes1, Maria del Carmen Garcia de Leon, Gustavo Varela-Fascinetto

  • 1Department of Experimental Medicine, School of Medicine, Universidad Nacional Autónoma de México, (UNAM), Hospital General de México, [corrected] Mexico City, Mexico.

Plos One
|April 28, 2010
PubMed

Insights

Cellular senescence, indicated by SA-betagal, p53, p16INK4a, and p21cip1, is present in children with end-stage liver disease, suggesting it’s linked to liver damage, not age.

Area of Science:

  • Hepatology
  • Cellular Biology
  • Pediatric Gastroenterology

Background:

  • Senescent cells are found in adult cirrhotic livers.
  • The role of senescence in pediatric end-stage liver disease is unclear.

Purpose of the Study:

  • To investigate cellular senescence and cell cycle checkpoint expression in pediatric end-stage liver disease.
  • To determine if senescence is age-dependent or associated with liver damage.

Main Methods:

  • Analysis of liver explants from five children (≤3 years) with end-stage liver disease (tyrosinemia, biliary atresia, fulminant hepatitis).
  • Assessed senescence-associated beta-galactosidase (SA-betagal) activity.
  • Evaluated expression of p16INK4a, p21cip1, and p53 cell cycle markers.

Main Results:

  • All pediatric liver samples showed positive SA-betagal staining in biliary ducts.
  • SA-betagal and p53 staining were prominent in ductular transformations in fulminant hepatitis.
  • p16INK4a and p21cip1 expression was observed in various liver cells and ducts in tyrosinemia and fulminant hepatitis cases.

Conclusions:

  • Cellular senescence in pediatric end-stage liver disease is associated with liver damage.
  • Senescence in this context does not appear to be an age-dependent phenomenon.
  • Further research is needed to correlate senescence markers with disease progression.
Abstract

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