Role of Hepatocyte Growth Regulators in Liver Regeneration

Abstract

We have studied whether growth factors, cytokines, hormones, neurotransmitters, and local hormones (autacoids) promote the proliferation of hepatic parenchymal cells (i.e., hepatocytes) using in vitro primary cultured hepatocytes. The indicators used for this purpose include changes in DNA synthesis activity, nuclear number, cell number, cell cycle, and gene expression. In addition, the intracellular signaling pathways from the plasma membrane receptors to the nucleus have been examined in detail for representative growth-promoting factors that have been found to promote DNA synthesis and cell proliferation of hepatocytes. In examining intracellular signaling pathways, the effects of specific inhibitors of presumed signaling factors involved have been pharmacologically confirmed, and the phosphorylation activities of the signaling factors (e.g., RTK, ERK, mTOR, and p70 S6K) have been evaluated. As a result, it has been found that there are many factors that promote the proliferation of hepatocytes (e.g., HGF, EGF, TGF-α, IL-1β, TNF-α, insulin, growth hormone (GH), prostaglandin (PG)), and serotonin (5-HT)), while there are very few factors (e.g., TGF-β1 and glucocorticoids) that inhibit the effects of growth-promoting factors. We have also found that 5-HT and GH promote the proliferation of hepatocytes via different autocrine factors (e.g., TGF-α and IGF-I, respectively). Using primary cultured hepatocytes, it will be possible to further study the molecular and cellular aspects of liver regeneration.

Mapping Cellular Interactions from Spatially Resolved Transcriptomics Data

“…This observation also resonates with the regulation of TGFβ/VEGF/PDGF pathways as shown in Fig. 6b , which are all important for hepatocyte homeostasis 54 . On the sending side, we observed that the autophagy of γδ T cells impacts both the apoptosis of liver cancer cells and the mTOR pathway of healthy hepatocytes.…”

Nutritionally Important Pro-Health Active Ingredients and Antioxidant Properties of Fruits and Fruit Juice of Selected Biennial Fruiting Rubus idaeus L. Cultivars

“…Leucine represents the group of branched-chain amino acids (BCAAs); together with isoleucine and valine, they constitute approximately 35% of essential amino acids [75,76]. These amino acids stimulate glucose transport [77,78] and regulate gene expression and hepatocyte cell-cycle pathways [79,80]. The other dominant amino acid in the present study was arginine.…”

Signaling pathways of liver regeneration: Biological mechanisms and implications

“…TNF-α participates in numerous liver biological responses and exerts a critical effect on hepatitis, liver fibrosis, liver failure, and LR. 57 , 58 , 59 , 60 After PHx, TNF-α activates NF-κB by binding to TNFR-1, which translocates NF-κB into the nucleus and induces IL-6 expression, subsequently, IL-6 activates STAT3 to promote LR. 61 When TNF-α is blocked, the production of IL-6 and LR will be inhibited.…”