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Role of the p38 MAP-Kinase Signaling Pathway for Cx32 and Claudin-1 in the Rat Liver

机译:p38 MAP激酶信号通路对Cx32和Claudin-1在大鼠肝脏中的作用

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Liver regeneration and cholestasis are associated with adaptive changes in expression of gap and tight junctions through signal transduction. The roles of stress responsitive MAP-kinase, p38 MAP-kinase, in the signaling pathway for gap junction protein, Cx32, and tight junction protein, claudin-1, were examined in rat liver in vivo and in vitro, including regeneration following partial hepatectomy and cholestasis after common bile duct ligation. Changes in the expression and function of Cx32 and claudin-1 in hepatocytes in vivo were studied using the p38 MAP-kinase inhibitor SB203580. Following partial hepatectomy and common bile duct ligation, down-regulation of Cx32 protein was inhibited by SB203580 treatment, Up-regulation of claudin-1 protein was enhanced by SB203580 treatment after partial hepatectomy but not common bile duct ligation. However, no change of the Ki-67 labeling index (which is a marker for cell proliferation) in the livers treated with SB203580, was observed compared to that without SB203580 treatment. In primary cultures of rat hepatocytes, however, treatment with a p38 MAP-kinase activator, anisomycin, decreased Cx32 and claudin-1 protein levels. p38 MAP-kinase may be an important signaling pathway for regulation of gap and tight junctions in hepatocytes. Changes of gap and tight junctions during liver regeneration and cholestasis are shown to be in part controlled via the p38 MAP-kinase signaling pathway and arc independent of cell growth.
机译:肝再生和胆汁淤积与通过信号转导的间隙和紧密连接的表达的适应性变化有关。在大鼠体内和体外检测了应激反应性MAP激酶p38 MAP激酶在间隙连接蛋白Cx32和紧密连接蛋白claudin-1的信号传导途径中的作用,包括部分肝切除术后的再生胆总管结扎后胆汁淤积和胆汁淤积使用p38 MAP激酶抑制剂SB203580研究了体内肝细胞中Cx32和claudin-1的表达和功能的变化。在部分肝切除和胆总管结扎后,SB203580处理可抑制Cx32蛋白的下调;在部分肝切除后通过SB203580处理可增强claudin-1蛋白的上调,但不对胆总管结扎。但是,与未使用SB203580处理的肝脏相比,未观察到用SB203580处理的肝脏的Ki-67标记指数(这是细胞增殖的标志)的变化。然而,在大鼠肝细胞的原代培养中,用p38 MAP激酶激活剂茴香霉素处理可降低Cx32和claudin-1蛋白水平。 p38 MAP激酶可能是调节肝细胞间隙和紧密连接的重要信号通路。肝脏再生和胆汁淤积过程中间隙和紧密连接的变化显示出部分受p38 MAP激酶信号通路控制,并且与细胞生长无关。

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