| Research Abstract |
Gap junctional intercellular communication (GJlC) via gap junctions is thought to play a crucial role in cell growth and cell differentiation. Although it is well known that marked expression and function of hepatic gap junctions was transiently decreased during liver regeneration after partial hepatectomy and liver injury, the mechanisms are still unclear. Because more recently, claudins, that formed tight junction structures, were found, the detail changes were never examined. On the other hand, the signal transduction pathways and activation of the mitogen-activated protein (MAP)-kinase, p38 MAP-kinase or phosphoinositol 3-kinase (PI3-kinase) signaling cascade may regulate proliferation and differentiation in hepatocytes.
In this study, to investigate the role of gap and tight junctions during liver regeneration, we performed the experiments using cultured hepatocytes. In treatment with MAP-kinase, p38 MAP-kinase or PI3-kinase inhibitors (PD98059, SB203580, LY294002) before the onset of DNA synthesis of primary rat hepatocytes, PI3-kinase pathway rather than the MAP-kinase and p38 MAP-kinase pathway plays an important role for proliferation of rat hepatocytes, and changes of gap and tight junctions during DNA synthesis in hepatocytes may be in part controlled through MAP-kinase and p38 MAP-kinase. Furthermore, we examined changes in localization of the tight junction proteins at all stages of cell division in mouse hepatic cell lines. In late telophase, the integral tight junction proteins occludin and claudin-1 were concentrated in the midbody between the daughter cells.
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