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Ablation of stellate cells during liver regeneration blocks mitosis and induces a switch in stellate cell phenotype
Author(s) -
Nejak-Bowen Kari N,
Orr Anne V,
Bowen William C,
Michalopoulos George K
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.274.6
Subject(s) - hepatic stellate cell , gliotoxin , apoptosis , microbiology and biotechnology , liver regeneration , biology , tunel assay , hepatocyte growth factor , cell growth , hepatocyte , regeneration (biology) , chemistry , endocrinology , immunology , receptor , biochemistry , in vitro , aspergillus fumigatus
Hepatic stellate cells (HSCs) synthesize new hepatocyte growth factor (HGF) during liver regeneration (LR), and also play an important function in matrix production; thus, we hypothesize that HSCs are the master regulators of LR. Rats were injected with either gliotoxin (which induces HSC apoptosis) or DMSO one day before and simultaneous with partial hepatectomy (PH). There were more apoptotic cells in the gliotoxin livers as compared to DMSO livers, as assessed by TUNEL staining. Ki67 staining show the presence of many proliferating cells in the control, while in the gliotoxin‐treated rats, mitosis was absent. Although HGF mRNA expression was unchanged, HGF protein expression was significantly decreased in the gliotoxin livers. Chronic elimination of stellate cells over a period of 5 days after PH also causes decreased proliferation and increased apoptosis. Intriguingly, this treatment induced a switch in HSC phenotype, with higher expression of alpha‐SMA in control rats compared to gliotoxin rats, which had more desmin. Finally, there was a paradoxical increase in both hepatocyte proliferation and apoptosis when HSCs were ablated during the later stages of LR. Thus, gliotoxin treatment at early time points after PH causes a block in proliferation and an increase in apoptosis, while treatment during the latter stages of LR causes a phenotypic change in HSC marker expression and an increase in proliferation.