EXPRESSION OF LEUKEMIA INHIBITORY FACTOR AND ITS RECEPTOR DURING LIVER-REGENERATION IN THE ADULT-RAT

Leukemia inhibitory factor (LIF) is a polyfunctional cytokine that was discovered in the conditioned medium from Buffalo rat liver cells. In the liver, LIF is known to induce acute phase proteins in the hepatoc ytes. No comprehensive study has yet been performed on the physiologic al role of this cytokine during liver regeneration. Thus, we studied t he level of expression and cellular distribution of transcripts for LI F, its receptor (LIFR), and signal transducing subunit gp130 during ra t liver regeneration after both simple partial hepatectomy (PH) and th e oval cell activation induced by the combination of 2-acetylaminofluo rene and PH. In addition, the expression of an acute phase protein alp ha 1-acidglycoprotein was examined. The level of transcripts for LIF a nd its receptor subunits increased and remained elevated during oval c ell expansion. In contrast, after PH, the transcripts were induced onl y transiently, showing a peak 24 hours after the operation. LIF and re ceptor subunits were expressed in both parenchymal and nonparenchymal fractions in the 2-acetylaminoiluorene/PH model, but the level of expr ession was most pronounced in the nonparenchymal fraction. In situ hyb ridization clearly revealed a strong expression of LIF, LIFR, and gp13 0 in the oval cells and demonstrated only a weak expression in the par enchyma. Interestingly, transcripts of alpha 1-acidglycoprotein were e xclusively detected in the parenchyma. These results suggest a phenoty pic difference between oval cells and hepatocytes in their signaling t hrough gp130. We hypothesize that the LIF/LIFR gp130 system may be inv olved in the expansion and differentiation of the liver stem cell comp artment.