Liver Specific Ablation of Integrin Linked Kinase in Mice Results in Enhanced and Prolonged cell proliferation After Phenobarbital Administration

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This study investigates the role of ILK in hepatocyte proliferation induced by Phenobarbital (PB). WT (wild type) and ILK‐/‐ mice were given PB( 0.1% in drinking water) for 10 days. Livers were harvested on 2, 5 and 10 day during PB administration. In the ILK‐/‐ mice the liver/body weight ratio was more than double as compared to 0h at day 2 and 5 while at day 10 it was thrice. In the WT mice the increase was not dramatic and seems to have leveled off after day 2. There were slightly increased PCNA positive cells in the ILK‐/‐ 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 but the ILK‐/‐ mice still had PCNA positive cells at day 5 and 10 suggesting a prolonged proliferative response. ILK‐/‐ mice also showed increased expression of key genes involved in hepatocyte proliferation at different time points during PB administration. In summarize, 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 have prolonged proliferative response to a mitogenic stimuli suggesting defect termination of proliferative response.The work is supported by a R01 grant (5R01CA035373‐26) titled "HGF in Liver Development, Regeneration and Neoplasia"