Modulation of hepatocyte function by changing the cell shape in primary culture

Abstract

To study the role of cell shape in control of hepatocyte function, we have developed a system that can quantitatively control the spreading of cultured rat hepatocytes using poly[2-hydroxyethyl methacrylate]. When hepatocytes were cultured in a dish coated with high concentration of poly[2-hydroxyethyl methacrylate] solution, formation of stress fibers were suppressed and they continued to have a compact shape. In the compact-shaped hepatocytes, the ability to induce tyrosine aminotransferase with dexamethasone remained high for longer periods of time, as compared to the hepatocytes that spread following culture in the polystyrene dish. Conversely, the hepatocytes showed more active DNA synthesis when they assumed a flat shape as a result of spreading. When the hepatocytes that had spread following long-term culture in the polystyrene dishes were treated with cytochalasin to induce depolymerization of F-actin, the ability of the cells to induce tyrosine aminotransferase upon stimulation with dexamethasone improved markedly. This effect was not altered by treatment with actinomycin D but was completely suppressed by cycloheximide, suggesting that microfilaments are involved in the post-transcriptional process of tyrosine aminotransferase induction. Thus, there is a possibility that F-actin rather than cell shape might regulate cellular function in primary cultured hepatocytes.