细胞谱系示踪技术在肝脏纤维化上皮-间质转化研究中的应用

Cell lineage tracing in study of epithelial-to-mesenchymal transition during hepatic fibrosis

肝脏纤维化是多种慢性肝脏损伤共同的病理过程.通过免疫组织化学技术研究人和动物样本证实,在慢性损伤肝脏纤维化过程中,一些肝脏细胞可发生上皮-间质转化(epithelial-to-mesenchymal transition,EMT)促进肝脏纤维化.然而免疫组织化学技术存在许多技术上的缺陷,导致肝脏纤维化过程中存在EMT的观点饱受质疑.细胞谱系示踪技术为研究器官发育、组织损伤修复以及单细胞的分化命运提供了重要的手段.近些年,随着基因工程技术的飞速发展,细胞谱系示踪技术也有所突破,尤其是诱导性重组酶Cre/loxp系统的应用,极大地拓宽了细胞谱系示踪技术的应用范围.目前,该技术越来越多的应用于研究肝脏纤维化过程中的EMT.本文将近来来细胞谱系示踪技术在判断肝脏纤维化过程中是否发生EMT的实验研究作一综述.

Hepatic fibrosis is the common pathologic process of chronic liver injury. Early studies mostly used immunohistochemistry to assess the role of epithelial-to-mesenchymal transition(EMT) in human or animal liver repair, and several types of liver cells including hepatocytes, cholangiocytes, hepatic stellate cells(HSCs) and liver progenitor cells have been shown to undergo EMT during hepatic fibrosis.However, this technique has several flaws. In recent years, with the rapid development of genetic engineering, especially the application of the recombinant enzyme Cre/loxP system,cell lineage tracing is becoming a popular and powerful tool to overcome the limitations of immunostaining for identifying EMT during hepatic fibrosis. Since this technique genetically labels cells, the marker will be present in any progeny of the labeled cells. Many groups have generated different lineages of double transgenic(DTG) mice and utilized different models of hepatic injury to investigate whether EMT contributes to hepatic injury or not. The purpose of this article is to summarize evidence,which is obtained using lineage cell tracing, for and against the possibility that EMT is involved in hepatic fibrosis.