Hepatocyte transplantation activates hepatic stellate cells with beneficial modulation of cell engraftment in the rat
Hepatocyte transplantation activates hepatic stellate cells with beneficial modulation of cell engraftment in the rat
复制标题
DOI：
10.1002/hep.20889
复制
发表时间：
2005-11-01
期刊：
影响因子：
13.5
通讯作者：
Gupta, S
中科院分区：
文献类型：
--
作者：
Benten, D;Kumaran, V;Gupta, S
我们研究了移植的肝细胞是否与肝星状细胞相互作用，因为细胞与细胞的相互作用可以调节它们在肝脏中的植入。我们将 Fischer 344 大鼠肝细胞移植到同源二肽中。肽酶 IV 缺陷大鼠。通过组织学方法或聚合酶链反应，通过基因表达的变化来分析肝星状细胞的激活，包括结蛋白和α-平滑肌肌动蛋白、基质蛋白酶及其抑制剂、生长因子和其他星状细胞相关基因。此外，还研究了肝缺血、库普弗细胞和细胞因子释放在肝星状细胞活化中的潜在作用。肝细胞移植激活结蛋白阳性肝星状细胞以及库普弗细胞，包括移植细胞附近的细胞。钆对库普弗细胞的抑制作用。氯化物、依那西普阻断肿瘤坏死因子α（TNF-α）活性或用硝酸甘油减轻肝缺血并不能减少这种肝星状细胞扰动。细胞移植后，能够激活肝星状细胞的可溶性信号被迅速诱导，同时基质金属蛋白酶-2、-3、-9、-13、-14及其抑制剂的早期表达上调。此外，用胶霉毒素预先消耗活化的肝星状细胞会减少移植细胞的植入。总之，细胞移植激活了肝星状细胞，进而促进了移植细胞在肝脏中的植入。肝星状细胞的操作可能为增强移植细胞植入后改善肝脏再生提供新策略。本文的补充材料可以在 HEPATOLOGY 网站 (http://interscience.wiley.com/Jpages/0270-9139/supmat/index.html) 上找到。
We investigated whether transplanted hepatocytes interact with hepatic stellate cells, as cell-cell interactions could modulate their engraftment in the liver. We transplanted Fischer 344 rat hepatocytes into syngeneic dipeptidyl. peptidase IV-deficient rats. Activation of hepatic stellate cells was analyzed by changes in gene expression, including desmin and a-smooth muscle actin, matrix proteases and their inhibitors, growth factors, and other stellate cell-associated genes with histological methods or polymerase chain reaction. Furthermore, the potential role of hepatic ischemia, Kupffer cells, and cytokine release in hepatic stellate cell activation was investigated. Hepatocyte transplantation activated desmin-positive hepatic stellate cells, as well as Kupffer cells, including in proximity with transplanted cells. Inhibition of Kupffer cells by gadolinium. chloride, blockade of tumor necrosis factor alpha (TNF-alpha) activity with etanercept or attenuation of liver ischemia with nitroglycerin did not decrease this hepatic stellate cell perturbation. After cell transplantation, soluble signals capable of activating hepatic stellate cells were rapidly induced, along with early upregulated expression of matrix metafloproteinases-2, -3, -9, -13, -14, and their inhibitors. Moreover, prior depletion of activated hepatic stellate cells with gliotoxin decreased transplanted cell engraftment. In conclusion, cell transplantation activated hepatic stellate cells, which, in turn, contributed to transplanted cell engraftment in the liver. Manipulation of hepatic stellate cells might provide new strategies to improve liver repopulation after enhanced transplanted cell engraftment. Supplementary material for this article can befound on the HEPATOLOGY website (http://interscience.wiley.com/Jpages/0270-9139/suppmat/index.html).