Increased Expression of Insulin-Like Growth Factor-II/ Mannose-6-Phosphate Receptor in Regenerating Rat Liver*

Abstract

This study examined the effect of two thirds hepatectomy on rat liver insulin-like growth factor-II (IGF-II) receptors and IGF-II receptor messenger RNA (mRNA) levels. IGF-II receptor levels were determined in liver plasma membrane and Golgi/endosome fractions from sham-operated and hepatectomized rats by ligand binding and immunoblotting after electrophoresis. After hepatectomy, IGF-II receptors increased initially in the plasma membrane (within 24 h of surgery) to 4-fold control levels, remained elevated for 72 h, and declined to control levels at 120 h when liver regeneration is near complete. However, Golgi/endosome levels of IGF-II receptors did not increase until 48 h, showing a maximum increase of 3.5-fold at 72 h after surgery and returning to control values at 120 h. The 9-kilobase mRNA for IGF-II receptor, determined by slot blotting with a complementary DNA probe, increased 2.5-fold within 24 h of surgery, attaining a maximum stimulation of 4-fold at 48 h, and then decreasing to normal levels by 120 h. These changes show that, after partial hepatectomy, IGF-II receptors increase rapidly at the cell surface, possibly due to receptor translocation from intracellular pools. This is followed by an increase of IGF-II receptor mRNA and increased receptor synthesis, resulting in an increase in total cellular receptors. These results suggest a role for IGF-II receptors in regenerating liver, perhaps in cell proliferation and/or in tissue remodeling.