Hepatocyte proliferation/growth arrest balance in the liver of mice during E. multilocularis infection: a coordinated 3-stage course.
Hepatocyte proliferation/growth arrest balance in the liver of mice during E. multilocularis infection: a coordinated 3-stage course.
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多房肠球菌感染期间小鼠肝脏中肝细胞增殖/生长停滞平衡：协调的三阶段过程。
DOI：
10.1371/journal.pone.0030127
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Lin R
中科院分区：
文献类型：
--
作者：
Zhang C;Wang J;Lü G;Li J;Lu X;Mantion G;Vuitton DA;Wen H;Lin R
泡球蚴病（AE）的特征是棘球蚴（E.）多房的在感染的各个阶段，在肝脏中发育的蠕虫寄生虫对感染肝脏的肝细胞中的增殖/生长停滞代谢途径的影响知之甚少。采用Western blot、qPCR和免疫组化方法检测了小鼠AE模型中MAPKs活化、Cyclins、PCNA、Gadd 45 β、Gadd 45 γ、p53和p21在感染后2 - 360天的表达水平。在早期（2-60 d）和中期（60 -180 d），CyclinB 1和CyclinD 1基因表达增加至30 d，60 d后恢复至对照水平; Gadd 45 β、CyclinA和PCNA表达持续增加; ERK 1/2被永久激活。p53、p21、Gadd 45 γ基因表达及caspase 3活性呈时间依赖性增加。感染后期（180 -360 d），p53、p21和Gadd 45 γ基因表达明显增强，JNK和caspase 3被激活。TUNEL分析显示肝细胞凋亡。CyclinE、p53 mRNA和p-p38表达在任何时间均无显著变化。我们的数据支持代谢途径的顺序激活的概念，其1）首先有利于寄生虫，肝脏和免疫细胞增殖和存活，从而促进宿主的后绦虫生育力和耐受性，以及2）然后有利于肝损伤/凋亡，蛋白质合成和外源性代谢的损伤，以及促进免疫缺陷，从而在后绦虫获得生育力后有助于原绦虫的传播。这些发现合理解释了肝肿大的临床观察结果和AE患者在主要肝切除术后的意外存活，以及慢性肝损伤、坏死和晚期肝衰竭和实验动物。
Alveolar echinococcosis (AE) is characterized by the tumor-like growth of Echinococcus (E.) multilocularis. Very little is known on the influence of helminth parasites which develop in the liver on the proliferation/growth arrest metabolic pathways in the hepatocytes of the infected liver over the various stages of infection. Using Western blot analysis, qPCR and immunohistochemistry, we measured the levels of MAPKs activation, Cyclins, PCNA, Gadd45β, Gadd45γ, p53 and p21 expression in the murine AE model, from day 2 to 360 post-infection. Within the early (day 2–60) and middle (day60–180) stages, CyclinB1 and CyclinD1 gene expression increased up to day30 and then returned to control level after day60; Gadd45β, CyclinA and PCNA increased all over the period; ERK1/2 was permanently activated. Meanwhile, p53, p21 and Gadd45γ gene expression, and caspase 3 activation, gradually increased in a time-dependent manner. In the late stage (day180–360), p53, p21 and Gadd45γ gene expression were significantly higher in infected mice; JNK and caspase 3 were activated. TUNEL analysis showed apoptosis of hepatocytes. No significant change in CyclinE, p53 mRNA and p-p38 expression were observed at any time. Our data support the concept of a sequential activation of metabolic pathways which 1) would first favor parasitic, liver and immune cell proliferation and survival, and thus promote metacestode fertility and tolerance by the host, and 2) would then favor liver damage/apoptosis, impairment in protein synthesis and xenobiotic metabolism, as well as promote immune deficiency, and thus contribute to the dissemination of the protoscoleces after metacestode fertility has been acquired. These findings give a rational explanation to the clinical observations of hepatomegaly and of unexpected survival of AE patients after major hepatic resections, and of chronic liver injury, necrosis and of hepatic failure at an advanced stage and in experimental animals.
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DOI：
10.1097/00042737-200012030-00011
发表时间：
2000-03-01
影响因子：
2.1
作者：
Bresson-Hadni, S;Vuitton, DA;Miguet, JP
通讯作者：
Miguet, JP
影响因子：
13.5
作者：
Fausto, N;Campbell, JS;Riehle, KJ
通讯作者：
Riehle, KJ
影响因子：
4.6
作者：
GOTTSTEIN, B;WUNDERLIN, E;TANNER, I
通讯作者：
TANNER, I
影响因子：
3.7
作者：
Berres, Marie-Luise;Trautwein, Christian;Wasmuth, Hermann E.
通讯作者：
Wasmuth, Hermann E.
影响因子：
64.8
作者：
De Smaele, E;Zazzeroni, F;Franzoso, G
通讯作者：
Franzoso, G