Characterization of cytokeratin 19-positive hepatocyte foci in the regenerating rat liver after 2-AAF/CCl4 injury.
Partial hepatectomy or carbon tetrachloride (CCl4) injury, following treatment of rats with 2-acetylaminofluorene (2-AAF) to inhibit proliferation of hepatocytes, induces proliferation of oval cells and possibly their differentiation into nodular foci of hepatocytes when higher doses of 2-AAF are used. Unfortunately, immunohistochemistry in previous studies failed to show oval cell markers in these foci, and thereby to demonstrate the precursor-product relationship between oval cells and hepatocytes. Immunohistochemistry on livers of rats treated with high dose 2-AAF/CCl4 was used. We found 7.6% of the hepatocyte foci were positive for an oval cell marker cytokeratin 19 (CK-19). These foci were positive for alpha-fetoprotein, less positive for carbamoylphosphate synthetase 1, and more positive for laminin in the basement membrane lining. Rarely present transitional foci had weaker expression of CK-19 and discontinuous laminin. Focal hepatocyte differentiation of oval cells was characterized by cell hypertrophy, membranous CK-19, and positive hepatocyte nuclear factor 4 (HNF-4). HNF-4+ small oval cells surrounding CK-19+ foci were frequently seen, suggesting that a paracrine mechanism(s) may be responsible for the enlargement of CK-19+ foci. In conclusions, oval cells appear to differentiate to CK-19+ foci and then to CK-19- foci in the high dose 2-AAF/CCl4 model.
The Graduate Institute of Applied Science and Engineering, Fu-Jen Catholic University, No. 510 Chung Cheng Rd, Hsinchuang, Taipei County, 24205, and Department of Internal Medicine, National Taiwan University Hospital, Taiwan.
Chien-Chang
CC
Chiu
Guan-Tarn
GT
Huang
Shiu-Huey
SH
Chou
Chiang-Ting
CT
Chien
Ling-Ling
LL
Chiou
Mei-Hwei
MH
Chang
Hsuan-Shu
HS
Lee
Ding-Shinn
DS
Chen
D015073:2-Acetylaminofluorene / Q000008:administration & dosage*; D000284:Administration, Oral; D000818:Animals; D002251:Carbon Tetrachloride / Q000008:administration & dosage*; D049109:Cell Proliferation / Q000187:drug effects; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D007120:Immunochemistry; D053539:Keratin-19 / Q000032:analysis / Q000096:biosynthesis*; D008099:Liver / Q000187:drug effects* / Q000473:pathology; D008115:Liver Regeneration / Q000187:drug effects*; D008297:Male; D051381:Rats; D011916:Rats, Inbred F344; D013194:Staining and Labeling; D000509:alpha-Fetoproteins / Q000032:analysis / Q000096:biosynthesis
D053539:Keratin-19; D000509:alpha-Fetoproteins; D015073:2-Acetylaminofluorene; D002251:Carbon Tetrachloride