Changes in growth factor and cytokine expression in biliary obstructed rat liver and their relationship with delayed liver regeneration after partial hepatectomy
Changes in growth factor and cytokine expression in biliary obstructed rat liver and their relationship with delayed liver regeneration after partial hepatectomy
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DOI：
10.3748/wjg.v12.i13.2053
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发表时间：
2006-04-07
影响因子：
4.3
通讯作者：
Miyazaki, Masaru
中科院分区：
文献类型：
--
作者：
Makino, Hironobu;Shimizu, Hiroaki;Miyazaki, Masaru
目的：探讨梗阻性黄疸对肝部分切除术后肝再生的影响。肝细胞生长因子（HGF），其受体，c-Met，血管内皮生长因子（VEGF）和转化生长因子β 1应用定量逆转录聚合酶链反应（RT-PCR）技术检测胆道梗阻（BO）后肝组织和离体肝细胞中TGF-β 1 mRNA的表达使用LightCycler。还研究了结蛋白和α-平滑肌肌动蛋白（α-SMA）的免疫组织化学染色。结果：BO后14 d，肝组织TGF-β 1 mRNA水平显著升高，并随胆汁淤积时间延长而增加。HGF、VEGF有升高趋势，但无统计学意义。在细胞分离物中，发现TGF-β 1 mRNA主要存在于肝星状细胞（HSC）组分中。免疫组织化学研究显示BO后汇管区HSC（结蛋白阳性细胞）和活化HSC（α-SMA阳性细胞）数量增加。在肝切除模型中，与假手术大鼠相比，BO大鼠的肝再生延迟。结论：BO可诱导肝星状细胞增殖和活化，导致肝组织TGF-β 1 mRNA表达上调，HGF mRNA表达下调。这些改变的表达模式可能与梗阻性黄疸肝切除术后延迟的肝再生密切相关。(C)2006年，WJG出版社。All rights reserved.
Aim: To study the effects of obstructive jaundice on liver regeneration after partial hepatectomy.Methods: Hepatocyte growth factor (HGF), its receptor, c-Met, vascular endothelial growth factor (VEGF) and transforming growth factor-beta 1 (TGF-beta 1) mRNA expression in both liver tissue and isolated liver cells were investigated after biliary obstruction (BO) by quantitative reverse-transcription polymerase chain reaction (RT-PCR) using a LightCycler. Immunohistochemical staining for desmin and a-smooth muscle actin (alpha-SMA) was also studied. Regenerating liver weight and proliferating cell nuclear antigen (PCNA) labeling index, and growth factor expression were then evaluated after 70% hepatectomy with concomitant internal biliary drainage in BO rats or sham-operated rats.Results: Hepatic TGF-beta 1 mRNA levels increased significantly 14 days after BO, and further increased with duration of cholestasis. Meanwhile, HGF and VEGF tended to increase, but was not significant. In cell isolates, TGF-beta 1 mRNA was found mainly in the hepatic stellate cell (HSC) fraction. Immunohistochemical studies revealed an increased number of HSCs (desmin-positive cells) and activated HSCs (alpha-SMA-positive cells) in portal areas after BO. In a hepatectomy model, liver regeneration was delayed in BO rats, as compared to sham-operated rats. TGF-beta 1 mRNA was significantly up-regulated up to 48 h after hepatectomy, and the earlier HGF mRNA peak was lost in BO rats.Conclusion: BO induces HSCs proliferation and activation, leading to up-regulation of TGF-beta 1 mRNA and suppression of HGF mRNA in livers. These altered expression patterns may be strongly involved in delayed liver regeneration after hepatectomy with obstructive jaundice. (C) 2006 The WJG Press. All rights reserved.