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Liver regeneration after carbon tetrachloride injury in retrorsine‐exposed rats
Author(s) -
Best D. Hunter,
Coleman William B.
Publication year - 2007
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.21.5.a188-a
Subject(s) - carbon tetrachloride , ccl4 , progenitor cell , chemistry , regeneration (biology) , hepatocyte , liver regeneration , centrilobular necrosis , liver injury , endocrinology , medicine , stem cell , biochemistry , biology , microbiology and biotechnology , in vitro , organic chemistry
Liver regeneration after partial hepatectomy (PH) in rats exposed to the mito‐inhibitory agent retrorsine is accomplished through the proliferation and differentiation of small hepatocyte‐like progenitor cells (SHPC). The cell of origin and tissue niche for the SHPC is not known. We investigated the possibility that SHPC are localized to a specific zone of the liver by combining retrorsine treatment with the centrilobular specific toxin carbon tetrachloride (CCl 4 ). F344 rats were treated with retrorsine (30 mg/kg i.p.) at 6 and 8 weeks of age followed by CCl 4 treatment (1500 mg/kg i.p.) 5 weeks later. This dose of CCl 4 resulted in the destruction of 61 ± 4% of liver mass and elicited a regenerative response equivalent to that of PH. Livers from retrorsine‐exposed CCl 4 ‐treated rats exhibit SHPC proliferation similar to retrorsine‐exposed rats subjected to PH (RP). SHPC appear at 3 days post‐injection, continue to expand at 7 and 14 days post‐injection, and completely regenerate/restore the liver mass and structure in these animals by 30 days post‐injection. The magnitude of SHPC response observed in the undamaged periportal zone of the liver in these animals is slightly dampened (versus RP rats) by the loss of the centrilobular region. Together these data suggest that the progenitor cells that give rise to SHPC are not restricted to the centrilobular zone of the liver. Support: NIH CA78343 and T32 ES 017017.