Fig. 4

Sustained inhibition of hepatocyte proliferation resulted in more extensive oval cell expansion in an undifferentiated state but no hepatocyte differentiation. a DPPIV-chimeric lineage tracing system subjected to AAF/PH treatment followed by continuous AAF gavage daily for an additional 4 weeks (AAF/PH/AAF). b Mean liver/body weight ratios at 1, 2, and 4 weeks in AAF/PH and AAF/PH/AAF injuries. The liver/body weight ratios remained low through 4 weeks in AAF/PH/AAF injury, indicating impaired liver regeneration in this model. *P < 0.05, t-test, AAF/PH vs. AAF/PH/AAF at 4 weeks. c Quantification of proliferative activities of DPPIV(+) hepatocytes and oval cells at 1, 2, and 4 weeks in AAF/PH/AAF injury. d Representative images stained histochemically for GGT and with immunofluorescence for CK19 from different rats, demonstrating that continuous AAF treatment promoted a more extensive oval cell expansion with time. e Representative double-immunofluorescence images for DPPIV/OV6, CK19/C/EBPα, and OV6/laminin in serial liver sections at 1, 2, and 4 weeks demonstrate that oval cell proliferation diffusely infiltrated the liver parenchyma, was surrounded by thick laminin basements, and continued to express only the biliary/oval cell markers, OV6, CK19, and C/EBPα at 2 and 4 weeks. Original magnification: d 100×; e 200×. Scale bars: d 300 μm; e 100 μm