Figure 1.
Increased FoxM1B expression in regenerating liver of old tg mice stimulates hepatocyte entry into DNA synthesis and mitosis. (A) Graphic representation of hepatocyte BrdUrd incorporation during mouse liver regeneration. Graphically presented is the BrdUrd incorporation (DNA replication) at the indicated hours after PHx with 12-month-old wt (red), 12-month-old TTR-HFH-11B tg (green), or 2-month-old wt (blue) CD-1 mice. Two hours before the regenerating livers were harvested, the mice received an i.p. injection of BrdUrd and immunohistochemical staining was used to measure the BrdUrd-incorporation rate in regenerating liver sections as described previously (21). The mean of the number of BrdUrd-positive nuclei per 1,000 hepatocytes and SD were calculated for each time point as described in Materials and Methods. Shown is the BrdUrd immunostaining of liver sections at the S phase peak (40 h after PHx) from either 12-month-old wt mice (B) or 12-month-old tg mice (C), demonstrating that restoring FoxM1B levels elicited increased BrdUrd incorporation in regenerating liver of old tg mice. (D) Graphic representation of increased hepatocyte mitosis in regenerating livers of old tg mice at the peak of mitosis (48 h after PHx). In three regenerating livers at 48 h after PHx, hepatocyte mitosis is expressed as the mean ± SD of the number of mitotic figures found per 1,000 hepatocytes (21).