| Title | Liver Specific Ablation of Integrin Linked Kinase (ILK) in Mice Results in Enhanced and Prolonged Cell Proliferation and Hepatomegaly after Phenobarbital Administration. | | Author(s) | Donthamsetty S, Bowen W, Mars W, Bhave V, Luo JH, Wu C, Hurd J, Orr A, Bell A, Michalopoulos G | | Institution | Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261. | | Source | Toxicol Sci 2009 Nov 17. | | Abstract | We have recently demonstrated that disruption of ECM/Integrin signaling via elimination of Integrin linked kinase (ILK) in hepatocytes interferes with signals leading to termination of liver regeneration. This study investigates the role of ILK in liver enlargement induced by Phenobarbital (PB). WT (wild type) and ILK/Liver-/- mice were given PB (0.1% in drinking water) for 10 days. Livers were harvested on 2, 5 and 10 days during PB administration. In the hepatocyte-specific ILK/Liver-/- mice the liver/body weight ratio was more than double as compared to 0h at day 2 (2.5 times) while at day 5 and 10 it was enlarged three times. In the WT mice the increase was as expected from previous literature (1.8 times) and seems to have leveled off after day 2. There were slightly increased PCNA positive cells in the ILK/Liver-/- animals at day 2 as compared to WT after PB administration. In the WT animals the proliferative response had come back to normal by day 5 and 10. Hepatocytes of the ILK/Liver-/- mice continued to proliferate up until day 10. ILK/Liver-/- mice also showed increased expression of key genes involved in hepatocyte proliferation at different time points during PB administration. In summary, ECM proteins communicate with the signaling machinery of dividing cells via ILK to regulate hepatocyte proliferation and termination of the proliferative response. Lack of ILK in the hepatocytes imparts prolonged proliferative response not only to stimuli related to liver regeneration but also to xenobiotic chemical mitogens such as phenobarbital. | | Language | ENG | | Pub Type(s) | JOURNAL ARTICLE
| | PubMed ID | 19920070 |
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