Role of peroxisome proliferator-activated receptor-gamma (PPARγ) during liver regeneration in rats
Article first published online: 6 JUN 2008
© 2008 The Authors. Journal compilation © 2008 Journal of Gastroenterology and Hepatology Foundation and Blackwell Publishing Asia Pty Ltd
Journal of Gastroenterology and Hepatology
Volume 23, Issue 6, pages 930–937, June 2008
How to Cite
Yamamoto, Y., Ono, T., Dhar, D. K., Yamanoi, A., Tachibana, M., Tanaka, T. and Nagasue, N. (2008), Role of peroxisome proliferator-activated receptor-gamma (PPARγ) during liver regeneration in rats. Journal of Gastroenterology and Hepatology, 23: 930–937. doi: 10.1111/j.1440-1746.2008.05370.x
- Issue published online: 6 JUN 2008
- Article first published online: 6 JUN 2008
- Accepted for publication 25 September 2007.
- 15-deoxy-Δ12,14-prostaglandin J2 (15d-PGJ2);
- liver regeneration;
- peroxisome proliferator-activated receptor-gamma (PPARγ);
Background and Aim: Peroxisome proliferator-activated receptor-gamma (PPARγ), a member of the nuclear receptor superfamily, is widely expressed in adipocytes and other tissues, including the liver. Several reports have shown that PPARγ activation induced cell-cycle arrest and apoptosis in tumor cells. We investigated the role of the PPARγ/ligand system and the effect of the PPARγ agonist during liver regeneration.
Methods: Expression of PPARγ and serum levels of 15-deoxy-Δ12,14-prostaglandin J2 (15d-PGJ2) by enzyme immunoassay were evaluated in rats following partial hepatectomy (PH group). Further, the effect of the PPARγ agonist, pioglitazone, on liver regeneration (PH + PGZ group) was evaluated by proliferating cell nuclear antigen labeling index, relative liver weight, and expression of cell-cycle regulators.
Results: The number of PPARγ-stained hepatocytes decreased at 24 h (PH, 15.8 ± 2.2%; sham, 35.5 ± 2.4%; P < 0.001) and increased in the late phase of liver regeneration compared to the sham-operated group (P < 0.001 at 48–120 h). The peaks of serum 15d-PGJ2 (627.0 ± 91.1 pg/ml) and PPARγ expression (90.6 ± 3.1%) coincided in the late phase of liver regeneration. Also, oral administration of pioglitazone inhibited hepatocyte proliferation, in terms of the proliferating cell nuclear antigen (PCNA) labeling index and p27 expression during the late phase of liver regeneration, and caused a transient reduction in liver mass when compared to the PH group.
Conclusions: These results indicate that the PPARγ/ligand system may be one of the key negative regulators of hepatocyte proliferation and may be responsible for the inhibition of liver growth in the late phase of liver regeneration.