Hepatocyte nuclear factor 1β induced by chemical stress accelerates cell proliferation and increases genomic instability in mouse liver.

The liver has a considerable capacity of regeneration against the damage. The regulatory factors and molecular mechanism for the capacity are not fully appreciated. In developmental processes, hepatocyte nuclear factor 1β (HNF1β) is a cooperative factor for HNF6, which is a known stimulatory factor for hepatocyte proliferation after partial hepatectomy. We showed that carbon tetrachloride (CCl4)-induced liver injury up-regulated HNF1β, whereas the expression of HNF6 was not affected by the chemical stress, indicating unknown physiological roles of HNF1β against the chemical stress, not in cooperation with HNF6. To determine whether HNF1β has a novel function in the liver regeneration, we overexpressed HNF1β in the mouse liver by adenoviral gene delivery. We revealed that overexpression of HNF1β resulted in accelerated cell proliferation with the protein level up-regulation of plasminogen and plasmin, a converted active form of plasminogen, which play a pivotal role in liver regeneration inducing hepatocyt...