Oval cell response is attenuated by depletion of liver resident macrophages in the 2-AAF/partial hepatectomy rat.
Oval cell response is attenuated by depletion of liver resident macrophages in the 2-AAF/partial hepatectomy rat.
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2-AAF/部分肝切除大鼠中肝脏驻留巨噬细胞的消耗会减弱卵圆细胞反应
DOI：
10.1371/journal.pone.0035180
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Chen XP
中科院分区：
文献类型：
--
作者：
Xiang S;Dong HH;Liang HF;He SQ;Zhang W;Li CH;Zhang BX;Zhang BH;Jing K;Tomlinson S;van Rooijen N;Jiang L;Cianflone K;Chen XP
背景/目的巨噬细胞通过分泌炎症介质在肝细胞介导的肝再生中发挥重要作用。然而，关于常驻巨噬细胞在卵圆细胞介导的肝再生中的作用的信息很少。本研究旨在探讨巨噬细胞在2-乙酰氨基芴/部分肝切除（2-AAF/PH）诱导的大鼠卵圆细胞扩增中的作用。方法学/主要发现我们耗尽2-AAF/PH治疗的大鼠肝脏巨噬细胞注射脂质体包封氯膦酸盐48小时前PH。残余肝块的再生，以及卵圆细胞的增殖和分化进行了测量。我们发现，巨噬细胞耗竭大鼠的死亡率和肝脏转氨酶水平较高。我们还发现，消耗巨噬细胞产生了显着减少的EPCAM和PCK阳性卵圆细胞在免疫组化染色的肝切片后9天PH。同时，卵圆细胞分化也减弱作为巨噬细胞消耗的结果，作为大病灶的小嗜碱性肝细胞观察到9天后，在对照组大鼠肝切除术，而他们几乎没有在巨噬细胞消耗大鼠。因此，实时聚合酶链反应分析表明，白蛋白mRNA的表达较低的巨噬细胞耗尽的肝脏。然后我们评估巨噬细胞耗竭是否会影响肝脏产生刺激肝再生的细胞因子。我们发现，在肝切除术后的早期，巨噬细胞耗竭显著抑制了肿瘤坏死因子-α和白细胞介素-6的表达，沿着信号转导和转录激活因子3磷酸化的缺乏。结论巨噬细胞在卵圆细胞介导的2-AAF/PH模型肝再生中起重要作用。
Background/Aims Macrophages are known to play an important role in hepatocyte mediated liver regeneration by secreting inflammatory mediators. However, there is little information available on the role of resident macrophages in oval cell mediated liver regeneration. In the present study we aimed to investigate the role of macrophages in oval cell expansion induced by 2-acetylaminofluorene/partial hepatectomy (2-AAF/PH) in rats. Methodology/Principal Findings We depleted macrophages in the liver of 2-AAF/PH treated rats by injecting liposome encapsulated clodronate 48 hours before PH. Regeneration of remnant liver mass, as well as proliferation and differentiation of oval cells were measured. We found that macrophage-depleted rats suffered higher mortality and liver transaminase levels. We also showed that depletion of macrophages yielded a significant decrease of EPCAM and PCK positive oval cells in immunohistochemical stained liver sections 9 days after PH. Meanwhile, oval cell differentiation was also attenuated as a result of macrophage depletion, as large foci of small basophilic hepatocytes were observed by day 9 following hepatectomy in control rats whereas they were almost absent in macrophage depleted rats. Accordingly, real-time polymerase chain reaction analysis showed lower expression of albumin mRNA in macrophage depleted livers. Then we assessed whether macrophage depletion may affect hepatic production of stimulating cytokines for liver regeneration. We showed that macrophage-depletion significantly inhibited hepatic expression of tumor necrosis factor-α and interleukin-6, along with a lack of signal transducer and activator of transcription 3 phosphorylation during the early period following hepatectomy. Conclusions These data indicate that macrophages play an important role in oval cell mediated liver regeneration in the 2-AAF/PH model.
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影响因子：
4.1
作者：
Ju, C;Reilly, TP;Pohl, LR
通讯作者：
Pohl, LR
影响因子：
13.5
作者：
Fausto, N;Campbell, JS;Riehle, KJ
通讯作者：
Riehle, KJ
DOI：
10.1016/j.biocel.2003.08.004
发表时间：
2004-03-01
影响因子：
4
作者：
Lee, CM;Yeoh, GC;Olynyk, JK
通讯作者：
Olynyk, JK
影响因子：
12.4
作者：
Devey, Luke;Ferenbach, David;Wigmore, Stephen J.
通讯作者：
Wigmore, Stephen J.
影响因子：
25.7
作者：
Faa, G;Van Eyken, P;Desmet, VJ
通讯作者：
Desmet, VJ