In the retrorsine (RS)-based model of massive liver repopulation, preexposure to this naturally occurring alkaloid is sufficient to prime normal host parenchymal cells to be slowly replaced by transplanted normal hepatocytes. The basis for this striking effect is yet to be fully elucidated. In the present studies the possible involvement of cell senescence was investigated. Fischer 344 rats were treated according to the RS-based protocol for hepatocyte transplantation, i.e., two doses of RS, 2 weeks apart, and were killed at 4 or 8 weeks after treatment. Control groups were given saline. Expression of senescence-associated beta-galactosidase was greatly induced in hepatocytes exposed to RS. In addition, several other changes that have been related to cell senescence were observed: these included markers of persistent activation of a DNA damage response, an increased expression of mammalian target of rapamycin, and positive regulators of the cell cycle, together with the induction of p21 and p27 cyclin-dependent kinase inhibitors. Furthermore, RS treatment increased levels of interleukin-6 in the liver, consistent with the activation of a senescence-associated secretory phenotype.

Hepatocyte senescence in vivo following preconditioning for liver repopulation

SERRA, MARIA PAOLA;MARONGIU, FABIO;SINI, MARCELLA;LACONI, EZIO
2012-01-01

Abstract

In the retrorsine (RS)-based model of massive liver repopulation, preexposure to this naturally occurring alkaloid is sufficient to prime normal host parenchymal cells to be slowly replaced by transplanted normal hepatocytes. The basis for this striking effect is yet to be fully elucidated. In the present studies the possible involvement of cell senescence was investigated. Fischer 344 rats were treated according to the RS-based protocol for hepatocyte transplantation, i.e., two doses of RS, 2 weeks apart, and were killed at 4 or 8 weeks after treatment. Control groups were given saline. Expression of senescence-associated beta-galactosidase was greatly induced in hepatocytes exposed to RS. In addition, several other changes that have been related to cell senescence were observed: these included markers of persistent activation of a DNA damage response, an increased expression of mammalian target of rapamycin, and positive regulators of the cell cycle, together with the induction of p21 and p27 cyclin-dependent kinase inhibitors. Furthermore, RS treatment increased levels of interleukin-6 in the liver, consistent with the activation of a senescence-associated secretory phenotype.
CELL-CYCLE, HEPATOCELLULAR INJURY, PARTIAL-HEPATECTOMY, MOUSE-LIVER, RETRORSINE, RATS, GROWTH, TRANSPLANTATION, REPLACEMENT, MODEL
File in questo prodotto:
File Dimensione Formato  
2012 Serra (Hepatocyte senescence in vivo following preconditioning for liver repopulation).pdf

Solo gestori archivio

Tipologia: versione editoriale
Dimensione 1.65 MB
Formato Adobe PDF
1.65 MB Adobe PDF   Visualizza/Apri   Richiedi una copia

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11584/108152
Citazioni
  • ???jsp.display-item.citation.pmc??? 11
  • Scopus 21
  • ???jsp.display-item.citation.isi??? 19
social impact