AI Article Synopsis
- Gene expression in liver cells (hepatocytes) varies from the portal to central area of the liver lobule, but the reasons for this zonation are still unclear.
- A proposed model suggests that this zonal difference arises from two opposing signals: one from central vein endothelial cells activating a beta-catenin pathway and another from blood-borne molecules activating Ras-dependent pathways.
- These opposing signals create gradients that influence which enzymes and proteins are expressed in different regions of the liver lobule.
Article Abstract
Gene expression in hepatocytes within the liver lobule is differentially regulated along the portal to central axis; however, the mechanisms governing the processes of zonation within the lobule are unknown. A model for zonal heterogeneity in normal liver is proposed, based on observations of differential expression of genes in liver tumors from mice that harbor activating mutations in either Catnb (which codes for beta-catenin) or Ha-ras. According to the model, the regulatory control consists of two opposing signals, one delivered by endothelial cells of the central veins activating a beta-catenin-dependent pathway (retrograde signal), the other by blood-borne molecules activating Ras-dependent downstream cascades (anterograde signal). In conclusion, gradients of opposing signaling molecules along the portocentral axis determine the pattern of enzymes and other proteins expressed in hepatocytes of the periportal and pericentral domains of the liver lobule.
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| http://dx.doi.org/10.1002/hep.21082 | DOI Listing |
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