Triiodothyronine and interleukin-6 (IL-6) induce expression of HGF in an immortalized rat hepatic stellate cell line
Triiodothyronine and interleukin-6 (IL-6) induce expression of HGF in an immortalized rat hepatic stellate cell line
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DOI：
10.1034/j.1600-0676.2003.00827.x
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发表时间：
2003-06-01
影响因子：
6.7
通讯作者：
Oren, R
中科院分区：
文献类型：
--
作者：
Kariv, R;Enden, A;Oren, R
背景/目标：尽管三碘甲状腺原氨酸（T3）被认为是肝细胞的主要有丝分裂原，但在体外对肝细胞的增殖没有影响，并且在我们的研究中，仅在肝损伤期间诱导显著的体内肝细胞增殖。我们假设T3可能通过诱导肝脏中的其他细胞分泌肝有丝分裂原而间接影响肝细胞增殖。研究方法：体内研究：分别给大鼠注射脂多糖、T3及两者联合给药，用增殖细胞核抗原（PCNA）染色和核分裂指数测定肝细胞增殖。体外研究：将大鼠肝星状细胞系（HSC-6 T）与T3、IL-6和两者的组合一起培养，并且我们通过ELISA测量来评估这些细胞因子/激素组合对细胞增殖和对IL-6和HGF分泌的影响。RT-PCR检测甲状腺激素受体的表达。结果：在体内：T3，与脂多糖一起，在治疗的大鼠中，增加PCNA染色和肝细胞有丝分裂指数。体外：肝星状细胞系表达甲状腺激素受体α 1，但不表达β 1。星状细胞的增殖不受T3的影响，有或没有IL-6。T3对星状细胞系中IL-6的分泌水平没有影响。肝星状细胞培养T3和IL-6显示显着增加量分泌的HGF培养48小时后。结论：T3可能通过激活星状细胞中HGF的表达并与IL-6共同作用，在损伤过程中诱导肝细胞增殖。
Background/Aims: Despite its being considered a primary mitogen for hepatocytes, triiodothyronine (T3) has no effect on the proliferation of hepatocytes in vitro , and in our studies, induces significant in vivo hepatocyte proliferation only during liver injury. We hypothesized that T3 may affect hepatocytes proliferation indirectly, by inducing other cells in the liver to secrete hepatic mitogens. Methods: In vivo studies: Lipopolysaccharide, T3 and a combination of the two were injected into rats, and hepatocyte proliferation was determined by PCNA staining and mitotic index. In vitro studies: a rat hepatic stellate cell line (HSC-6T) was cultured with T3, IL-6 and a combination of the two, and we assessed the effect of these cytokine/hormone combinations on the cell proliferation and on secretion of IL-6 and HGF, measured by ELISA. Expression of thyroid hormone receptors was assessed by RT-PCR. Results: In vivo : T3, together with lipopolysaccharide, enhances PCNA staining and the mitotic index of hepatocytes in the treated rats. In vitro : the hepatic stellate cell line expresses thyroid hormone receptor alpha1, but not beta1. Proliferation of stellate cells is not affected by T3, with or without IL-6. T3 has no effect on secreted levels of IL-6 in the stellate cell line. Hepatic stellate cells cultured with T3 and IL-6 show significantly increased amounts of secreted HGF after 48 h in culture. Conclusion: T3 may induce hepatocyte proliferation in vivo during injury by turning on expression of HGF in stellate cells and acting together with IL-6.