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Pre-stimulated Mice with Carbon Tetrachloride Accelerate Early Liver Regeneration After Partial Hepatectomy.

Abstract：

BACKGROUND AND AIM:The liver has a high capacity of its regeneration. Most hepatic cells are quiescent unless otherwise stimulated such as their injury or ablation. A previous study suggest that pre-activated hepatic cells have a positive effect on their regeneration. In this study, we examined whether the pre-activated hepatic cells for regeneration accelerate the subsequent liver regeneration. METHODS:We administered a single injection of carbon tetrachloride (CCl4) to mice 7 days before partial hepatectomy (PHx). Liver weight/body weight ratio and several parameters for cell proliferation such as mitotic index and the number of Ki67 positive cells in the liver were examined after PHx as indexes of liver regeneration. RESULTS:Compared to control mice, those pre-stimulated with CCl4 showed earlier liver regeneration 48 h after PHx. Regardless of their accelerated regeneration, pre-stimulated mice showed less cell proliferation than did control mice during liver regeneration. Hepatic fibrosis was not observed in both control and CCl4-pretreated mice after PHx. Mice pre-treated with CCl4 showed the higher matrix metalloproteinase 9 (MMP9) expression than those pre-treated with olive oil. When matrix metalloproteinase 9 (MMP9) activity was inhibited, the pre-stimulated mice did not demonstrate accelerated liver regeneration and they returned to the original state for cell proliferations after PHx. CONCLUSIONS:Pre-activated liver by CCl4 promoted its subsequent regeneration after PHx. This was not a cause of fibrosis and partly dependent on MMP9 pre-activity rather than cell proliferation in liver. Our findings would not only provide a novel strategy for liver regeneration without cell proliferation as much as possible and also propose a new method for liver transplantation.

journal_name

Dig Dis Sci

journal_title

Digestive diseases and sciences

authors

Arioka Y,Ito H,Ando T,Ogiso H,Hirata A,Hara A,Seishima M

doi

10.1007/s10620-015-3536-9

subject

Has Abstract

pub_date

2015-06-01 00:00:00

pages

1699-706

issue

eissn

0163-2116

issn

1573-2568

journal_volume

pub_type

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Pre-stimulated Mice with Carbon Tetrachloride Accelerate Early Liver Regeneration After Partial Hepatectomy.