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Endogenous Interleukin 18 Suppresses Liver Regeneration After Hepatectomy in Mice.

内源性白细胞介素 18 抑制小鼠肝切除术后的肝再生。

  • 影响因子:2.65
  • DOI:10.1002/lt.25709
  • 作者列表:"Ma T","Zhang Y","Lao M","Chen W","Hu Q","Zhi X","Chen Z","Bai X","Dang X","Liang T
  • 发表时间:2020-03-01
Abstract

:The comprehensive role of interleukin (IL) 18 during liver regeneration is barely studied. Our aim is to evaluate the role of IL18 in liver regeneration after partial hepatectomy (PH) in mice. The expression profile of IL18 in the liver and the gut after 70% PH was measured. Liver samples after 70% and 85% PH from IL18 knockout (IL18-/- ) mice and wild type (WT) mice were collected for comparison of liver regeneration. The effect of recombinant IL18 on liver regeneration was tested in IL18-/- mice, and the utility of IL18 binding protein (BP) was also evaluated following 70% PH in WT mice. Expression levels of IL18 in the liver and the gut elevated after 70% PH. The liver weight/body weight ratios (LBWRs) after PH were significantly higher in IL18-/- mice than those in WT mice. Recombinant IL18 injection significantly decreased LBWR at 7 days after 70% PH in IL18-/- mice. The expression of cyclin D1, EdU labeling index, and Ki-67 proliferation index were much higher in IL18-/- mice than those in WT mice after 70% PH. The expression level of glypican 3 (GPC3) in WT mice significantly elevated during liver regeneration. In contrast, the expression level of GPC3 in IL18-/- mice remained roughly unchanged during liver regeneration. IL18BP injection significantly increased the LBWR at 7 days after 70% PH in WT mice. In conclusion, endogenous IL18 inhibited liver regeneration after PH in mice, possibly through up-regulating GPC3. IL18BP may be an effective agent to promote liver regeneration after PH.

摘要

: 白细胞介素 (IL) 18 在肝再生过程中的综合作用几乎没有研究。我们的目的是评价 IL18 在小鼠部分肝切除术 (PH) 后肝再生中的作用。测定 70% PH 后 IL18 在肝脏和肠道中的表达谱。收集 IL18 基因敲除 (IL18-/-) 小鼠和野生型 (WT) 小鼠 70% 和 85% PH 后的肝脏样本,用于比较肝再生。在 IL18-/-小鼠中测试了重组 IL18 对肝再生的影响,在 WT 小鼠中 70% PH 后也评估了 IL18 结合蛋白 (BP) 的效用。70% PH 后肝脏和肠道 IL18 的表达水平升高。PH 后 IL18-/-小鼠的肝重/体重比 (LBWRs) 显著高于 WT 小鼠。重组 IL18 注射在 IL18-/-小鼠 70% PH 后 7 天显著降低 LBWR。70% PH 后,IL18-/-小鼠 cyclin D1 、 EdU 标记指数和 Ki-67 增殖指数的表达明显高于 WT 小鼠。WT 小鼠肝再生过程中磷脂酰肌醇蛋白聚糖 3 (GPC3) 的表达水平显著升高。相比之下,IL18-/-小鼠在肝再生过程中 GPC3 的表达水平大致保持不变。IL18BP 注射显著增加了 WT 小鼠 70% PH 后 7 天的 LBWR。总之,内源性 IL18 抑制小鼠 PH 后的肝再生,可能通过上调 gpc3。IL18BP 可能是 PH 后促进肝再生的有效药剂。

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