Full‐length HGF mRNA persists after genetic recombination in mice

Abstract

Hepatocyte growth factor (HGF) has been shown to be indispensible for liver regeneration because it serves as the main mitogenic stimulus driving hepatocytes to proliferate. We hypothesize that ablating HGF in adult mice would have a deleterious effect on liver homeostasis. HGFflox/flox mice were bred to mice transgenic for either Mx‐cre or Tam‐cre and then treated with a regimen of either p(I):p(C) or tamoxifen, respectively. Analysis of liver genomic DNA from animals 10 days after treatment showed that a majority (70–80%) of the DNA underwent cre‐induced genetic recombination. Intriguingly, however, analysis by RT‐PCR showed the presence of both the unrecombined and recombined form of HGF mRNA after treatment. HGF protein levels were also unchanged between control and treated (KO) mice. Separation of liver cell populations into hepatocytes and non‐parenchymal cells showed equal recombination of HGF genomic DNA in both cell types. The presence of unrecombined HGF mRNA persisted in the liver even after 2/3 partial hepatectomy (PH). HGF protein expression in control and KO livers after PH was equivalent, correlating with the persistence of full‐length HGF mRNA. Additionally, ablation of HGF genomic DNA had no impact on proliferation during regeneration. Thus, HGF mRNA may be persisting due to long‐term mRNA stability or de novo production of full‐length HGF from unrecombined stellate cells.