The role of gap and tight junctions during liver regeneration

间隙和紧密连接在肝再生过程中的作用

• 批准号: 13670224
• 负责人: KOJIMA Takashi
• 金额: $ 2.3万
• 依托单位: Sapporo Medical University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13670224/
• 关键词: gap junction; tight junction; liver regeneration; proliferation; signal transduction; 肝細胞; 分化

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.

间隙连接细胞间通讯（GJlC）通过间隙连接被认为在细胞生长和细胞分化中起着至关重要的作用。虽然众所周知，肝间隙连接的显著表达和功能在部分肝切除术和肝损伤后的肝脏再生过程中会短暂下降，但其机制尚不清楚。因为最近才发现了形成紧密连接结构的克劳丁，所以细节变化从未被研究过。另一方面，丝裂原活化蛋白（MAP）激酶、p38 MAP激酶或磷酸肌醇3-激酶（pi3 -激酶）信号级联的信号转导途径和激活可能调节肝细胞的增殖和分化。在本研究中，为了研究间隙和紧密连接在肝脏再生中的作用，我们用培养的肝细胞进行了实验。在原代大鼠肝细胞DNA合成开始前用map -激酶、p38 map -激酶或pi3 -激酶抑制剂（PD98059、SB203580、LY294002）处理时，对大鼠肝细胞增殖起重要作用的是pi3 -激酶途径，而不是map -激酶和p38 map -激酶途径，肝细胞DNA合成过程中间隙和紧密连接的变化可能部分通过map -激酶和p38 map -激酶控制。此外，我们还研究了小鼠肝细胞系在细胞分裂的各个阶段紧密连接蛋白的定位变化。在晚期，完整的紧密连接蛋白occludin和claudin-1集中在子细胞之间的中间。

项目成果

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