Kariv R, Enden A, Zvibel Isab, Rosner G, Brill S, Shafritz D A, Halpern Z, Oren R
Liver Unit, Gastroenterology Institute, Tel Aviv Sourasky Medical Center, Weizmann 6, Tel Aviv, Israel.
Liver Int. 2003 Jun;23(3):187-93. doi: 10.1034/j.1600-0676.2003.00827.x.
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.
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.
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.
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 alpha 1, but not beta 1. 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.
T3 may induce hepatocyte proliferation in vivo during injury by turning on expression of HGF in stellate cells and acting together with IL-6.
背景/目的：尽管三碘甲状腺原氨酸（T3）被认为是肝细胞的主要促分裂原，但在体外对肝细胞增殖并无影响，且在我们的研究中，仅在肝损伤期间能诱导显著的体内肝细胞增殖。我们推测，T3可能通过诱导肝脏中的其他细胞分泌肝促分裂原，从而间接影响肝细胞增殖。
体内研究：将脂多糖、T3及二者的组合注射入大鼠体内，通过增殖细胞核抗原（PCNA）染色和有丝分裂指数测定肝细胞增殖情况。
用T3、白细胞介素-6（IL-6）及二者的组合培养大鼠肝星状细胞系（HSC-6T），通过酶联免疫吸附测定（ELISA）评估这些细胞因子/激素组合对细胞增殖以及IL-6和肝细胞生长因子（HGF）分泌的影响。通过逆转录聚合酶链反应（RT-PCR）评估甲状腺激素受体的表达。
体内研究：T3与脂多糖共同作用可增强处理组大鼠肝细胞的PCNA染色和有丝分裂指数。体外研究：肝星状细胞系表达甲状腺激素受体α1，但不表达β1。无论有无IL-6，T3均不影响星状细胞的增殖。T3对星状细胞系中IL-6的分泌水平无影响。在培养48小时后，用T3和IL-6培养的肝星状细胞分泌的HGF量显著增加。
T3可能通过开启星状细胞中HGF的表达并与IL-6共同作用，在损伤期间诱导体内肝细胞增殖。
