Résumé
The capacity of the liver to regenerate after a reduction in liver mass induced by surgical removal is quite remarkable. The most widely studied example of this phenomenon is accompanied by many investigators but the exact mechanism is not clear. Over the past decade, it has been demonstrated that growth factors play a major role in liver regeneration. Several growth factors such as epidermal growth factor, transforming growth factor(TGF), acidic fibroblast growth factor and hepatocyte growth factor(HGF) are involved in liver regeneration. Recently, HGF has aroused increasing interest due to its powerful mitogenic effect and multiple functions on various cell types. The receptor for HGF has recently been characterized as the product of the protooncogene c-met. We have examined the changes of synthesis of DNA and the expression of HGF mRNA and c-met mRNA that be involved in liver regeneration, after partial hepatectomy in the rat. Also we have examined the expression of TGF- mRNA that might be involved in inhibition of epithelial cell regeneration and differentiation of hepatocyte. Proliferative index was determined to use in vivo thymidine uptake. Nothern blot analysis used to assay HGF mRNA an TGF- mRNA. RNase protection assay used to assay c-met mRNA. The thymidine uptake of the remnant liver was abruptly increased after 18 hours, was maintained 24 hours. The nothern blot analysis showed that the expression of HGF mRNA and TGF- mRNA increased continuously within 24 hours. The RNase protection assay showed that the expression of c-met mRNA decreased continuously during one day after partial hepatectomy. The data presented here suggests that HGF is involved in liver regeneration and continuous decrease of c-met mRNA is phenomenon of receptor down-regulation. The increase of TGF- mRNA, well known as inhibitor of cell regeneration, suggests that TGF- is control mechanism of liver regeneration.
Sujets)
Animaux , Humains , Rats , ADN , Régulation négative , Facteur de croissance épidermique , Cellules épithéliales , Facteur de croissance fibroblastique de type 1 , Hépatectomie , Facteur de croissance des hépatocytes , Hépatocytes , Protéines et peptides de signalisation intercellulaire , Régénération hépatique , Foie , Régénération , Personnel de recherche , Ribonucléases , ARN messager , ThymidineRésumé
Isoenzymes of alkaline phosphatase from purified extracts of liver, intestine, pancreas and bone of rats were determined by their isoelectric points and compared with those from serum. 1) The extracts obtained from homogenized tissues were centrifuged at 65,000xg and filtered through an Ultrogel AcA 34 column. Among the three major peaks obtained by gel filtration, the second peak fractions were further separated by isoelectric focusing. Isoenzymes of alkaline phosphatase were found only in the second peak. 2) Isoenzymes of alkaline phosphatase were distinguishable with pH 3.5-10 ampholytes. When pH 3-6 ampholytes were used, isoenzymes were more clearly separated, e.g., 4in serum, 5 in intestine and 2 each in the liver, pancreas, and bone. 3) Comparing the bands of the isoenzymes of alkaline phosphatase to those of serum, only the band with 5.04 pI was the same between serum and intestine. These results indicate that several forms of alkaline phosphatase, even though all are from the rat, may exist; and some of the isoenzymes of alkaline phosphatase found in the serum originated from the intestine.