>From the Department of Biology, College of Sciences, Shiraz University, Shiraz, Iran.
Exp Clin Transplant. 2020 Apr;18(2):215-223. doi: 10.6002/ect.2017.0120. Epub 2018 Mar 9.
Toll-like receptors and downstream signal transduction pathways play pivotal roles in induction of inflammation, which is crucial for liver injury and regeneration.
Using a mouse model of partial hepatic ischemia-reperfusion injury followed by a 28-day time course for liver repair and regeneration, we assessed gene expression levels for Toll-like receptors, myeloid differentiation primary response 88, TIR-domain-containing adapter-inducing interferon-β, nuclear factor κB, interferon regulatory factors, tumor necrosis factor-α, and interleukins 1β and 6 at days 1, 4, 7, 14, and 28 after reperfusion in liver and blood cells by quantitative polymerase chain reaction.
Mouse liver was gradually injured until 24 hours after reperfusion, and necrotic areas remained for 7 days. Concurrent with liver necrosis, overexpression of hepatocyte growth factor in blood cells (days 1-14), transient overexpression of cyclin D1 at day 7 in hepatic cells, and overexpression of transforming growth factor-β1 at days 7 and 14 in blood cells were used to characterize the priming, proliferative, and termination phases of liver regeneration. Liver regeneration was associated with significant up-regulation of Toll-like receptor 4, p65, interferon regulatory factors 1, 3, 9, tumor necrosis factor-α, and interleukin 1β at 24 hours. Liver regeneration was also associated with persistent overexpression of MyD88 (days 1-28) and with delayed TIR-domain-containing adapter-inducing interferon-β (days 4-28) in hepatic cells. In peripheral blood cells, Toll-like receptor 2 and MyD88 were up-regulated at 24 hours and Toll-like receptor 4 (days 1-14) and interferon regulatory factor 1 (days 1-7) showed persistent overexpression concomitant with interferon regulatory factor 5 (days 7-14); interleukin 1β (days 1-28) and interleukin 6 (day 4-28) also showed persistent expression.
We depict for the first time a prospective view of cooperative transcriptional activation of Toll-like receptors/adaptors/interferon regulatory factors/cytokines in both liver and blood cells during different phases of liver repair after ischemia-reperfusion injury.
Toll 样受体及其下游信号转导途径在炎症诱导中发挥关键作用，炎症对于肝损伤和再生至关重要。
使用小鼠部分肝缺血再灌注损伤模型，并在肝修复和再生的 28 天时间过程中，我们通过定量聚合酶链反应评估了再灌注后第 1、4、7、14 和 28 天肝和血细胞中 Toll 样受体、髓样分化初级反应 88、TIR 结构域包含衔接诱导干扰素-β、核因子 κB、干扰素调节因子、肿瘤坏死因子-α 和白细胞介素 1β 和 6 的基因表达水平。
小鼠肝逐渐受损，直至再灌注后 24 小时，坏死区持续 7 天。随着肝坏死，血细胞中肝细胞生长因子的过度表达（第 1-14 天）、肝细胞中环化蛋白 D1 在第 7 天的短暂过度表达以及转化生长因子-β1 在血细胞中的过度表达在第 7 天和第 14 天用于描述肝再生的启动、增殖和终止阶段。肝再生与 Toll 样受体 4、p65、干扰素调节因子 1、3、9、肿瘤坏死因子-α 和白细胞介素 1β 在 24 小时的显著上调相关。肝再生还与肝细胞中 MyD88 的持续过度表达（第 1-28 天）和 TIR 结构域包含衔接诱导干扰素-β 的延迟（第 4-28 天）相关。在外周血中，Toll 样受体 2 和 MyD88 在 24 小时上调，Toll 样受体 4（第 1-14 天）和干扰素调节因子 1（第 1-7 天）显示持续过度表达，同时伴有干扰素调节因子 5（第 7-14 天）；白细胞介素 1β（第 1-28 天）和白细胞介素 6（第 4-28 天）也显示持续表达。
我们首次描绘了缺血再灌注损伤后肝修复不同阶段肝和血细胞中 Toll 样受体/衔接蛋白/干扰素调节因子/细胞因子的协同转录激活的前瞻性视图。
