Insulin-like growth factor 2 is a key mitogen driving liver repopulation in mice.
Insulin-like growth factor 2 is a key mitogen driving liver repopulation in mice.
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胰岛素样生长因子 2 是驱动小鼠肝脏再生的关键有丝分裂原
DOI：
10.1038/s41419-017-0186-1
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发表时间：
2018-01-18
影响因子：
9
通讯作者：
He ZY
中科院分区：
文献类型：
--
作者：
Wang MJ;Chen F;Liu QG;Liu CC;Yao H;Yu B;Zhang HB;Yan HX;Ye Y;Chen T;Wangensteen KJ;Wang X;Hu YP;He ZY
肝细胞移植在肝脏疾病的治疗中作为原位器官移植的替代方案具有很大的前景。然而，由于受体肝脏中肝细胞增殖的调节机制尚未得到很好的表征，因此尚未实现具有临床意义的肝脏再生水平。在遗传性酪氨酸血症I型小鼠模型中，富马酰乙酰乙酸水解酶缺陷型（Fah−/−）小鼠，我们发现宿主肝细胞中胰岛素样生长因子2（IGF 2）的表达水平逐渐增加。同样，在FAH活性缺乏的患者的肝脏中发现了高水平的IGF 2。重组IGF 2直接促进体外原代肝细胞增殖。通过阻断PI 3 K/Akt和MAPK途径抑制IGF 2表达可显著降低Fah −/−小鼠的肝脏再增殖水平。有趣的是，在肝细胞移植前用IGF 2治疗通常改善了在各种肝损伤小鼠模型中观察到的肝再生量。总之，这些发现强调了Fah −/−小鼠治疗性肝脏再生的潜在机制，并表明IGF 2是肝细胞移植治疗的潜在肝细胞有丝分裂原。
Hepatocyte transplantation holds great promise as an alternative to orthotopic organ transplantation in the treatment of liver diseases. However, obtaining clinically meaningful levels of liver repopulation has not been achieved because the mechanisms regulating hepatocyte proliferation in recipient livers have not yet been well characterized. In the mouse model of Hereditary Tyrosinemia Type I, the fumarylacetoacetate hydrolase-deficient (Fah−/−) mouse, we found gradually increasing expression level of insulin-like growth factor 2 (IGF2) in the hepatocytes of host livers. Similarly, high levels of IGF2 were found in the livers of patients with deficient FAH activity. Recombinant IGF2 directly promotes proliferation of primary hepatocytes in vitro. Inhibition on IGF2 expression through the interruption of PI3K/Akt and MAPK pathways significantly reduced the level of liver repopulation inFah−/−mice. Interestingly, treatment with IGF2 before hepatocyte transplantation generally improved the amount of liver repopulation seen in various mice models of liver injury. Altogether, these findings underscore the underlying mechanisms of therapeutic liver repopulation inFah−/−mice, and indicate that IGF2 is a potential hepatocyte mitogen for liver cell transplantation therapies.
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影响因子：
13.5
作者：
Vogel, A;van den Berg, IET;Grompe, M
通讯作者：
Grompe, M
影响因子：
25.7
作者：
Soltys KA;Soto-Gutiérrez A;Nagaya M;Baskin KM;Deutsch M;Ito R;Shneider BL;Squires R;Vockley J;Guha C;Roy-Chowdhury J;Strom SC;Platt JL;Fox IJ
通讯作者：
Fox IJ
影响因子：
13.5
作者：
Wang, Min-Jun;Chen, Fei;Hu, Yi-Ping
通讯作者：
Hu, Yi-Ping
DOI：
10.1007/978-1-4939-1453-1_3
发表时间：
2014-01-01
期刊：
ANIMAL MODELS FOR STEM CELL THERAPY
影响因子：
--
作者：
Krause, Petra;Rave-Frank, Margret;Koenig, Sarah
通讯作者：
Koenig, Sarah
DOI：
10.1073/pnas.1219079110
发表时间：
2013-04-09
影响因子：
11.1
作者：
Lui, Julian C.;Baron, Jeffrey
通讯作者：
Baron, Jeffrey