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上皮间质转化在人胚胎肝胆管板发育过程中的发生情况及其意义
徐军1*,周继2,张世芬2,王健1,胡勇1,余宏宇3
0
(1. 解放军105医院病理科, 合肥 230031;
2. 安徽省妇幼保健院妇产科, 合肥 230000;
3. 第二军医大学长征医院病理科, 上海 200003
*通信作者)
摘要:
目的 观察上皮间质转化(EMT)标记物在人胚胎肝胆管板发育过程中的表达, 探讨胆管板发育过程中EMT的发生和意义。方法 应用免疫组化法观察EMT相关标记物细胞角蛋白19 (CK19)、波形蛋白(vimentin)、α-平滑肌肌动蛋白(α-SMA)在31例8~40周龄人胚胎肝胆管板发育过程中的表达和变化情况。结果 从8周龄开始, 随着胆管板阶段、胆管板重新塑形阶段、胆管形成阶段的发展, 汇管区内CK19染色阳性细胞百分率也逐渐增加, 而vimentin和α-SMA阳性细胞百分率则逐渐减少, CK19染色阳性细胞百分率分别与vimentin和α-SMA阳性细胞百分率呈负相关(CK19与vimentin:r=-0.820, P<0.001; CK19与α-SMA:r=-0.797, P<0.001)。9周龄胚胎肝胆管板细胞开始表达vimentin, 13~19周时达到高峰, 之后减少, 28周时检测不到;14~32周龄胚胎肝部分发育中的胆管细胞也表达vimentin, 观察到汇管区vimentin阳性的肌纤维母细胞(pMFs)向胆管(板)内整合、移行。通过连续切片观察到 9~32周龄胚胎肝部分胆管板或胆管细胞共表达vimentin和CK19。结论 人胚胎肝胆管板发育过程中存在间质上皮转化,与胆管形成有关。
关键词:  肝干细胞  胚胎肝  胆管板  上皮间质转化  免疫组织化学
DOI:10.3724/SP.J.1008.2014.01378
投稿时间:2014-04-09修订日期:2014-05-23
基金项目:
Epithelial mesenchymal transition during the development of ductal plate in human liver and its significance
XU Jun1*,ZHOU Ji2,ZHANG Shi-fen2,WANG Jian1,HU Yong1,YU Hong-yu3
(1. Department of Pathology, No. 105 Hospital of PLA, Hefei 230031, Anhui, China;
2. Department of Gynecology and Obstetrics, Anhui Provincial Maternity and Child-care Hospital, Hefei 230000, Anhui, China;
3. Department of Pathology, Changzheng Hospital, Second Military Medical University, Shanghai 200003, China
*Corresponding author)
Abstract:
Objective To investigate the expression of markers for epithelial-mesenchymal transition (EMT) during the development of ductal plate in human liver, so as to discuss the role of EMT during ductal plate development in the liver. Methods Immunohistochemical method was used to examine the expression of EMT markers (CK19, vimentin, and α-SMA) in the liver tissues of 31 fetuses of 8-40 weeks old. Results From the 8th gestation week onwards (ductal plate phase, remodeling phase of ductal plate, and formation phase of bile ducts), the CK19-positive cells in the portal tract were gradually increased, vimentin/α-SMA-positive portal mesenchymal cells were gradually decreased, and CK19-positive cells were negatively correlated with vimentin/α-SMA expression ones (vimentin: r=-0.820, P<0.001; α-SMA: r=-0.797, P<0.001). The ductal plate cells began to express vimentin at the 9th week of gestation, the expression peaked in the fetal liver during 13-19 weeks of gestation, and then it was gradually declined and became undetectable at the 28th week. Some immature bile duct epithelial cells showed cytoplasmic immunostaining of vimentin from 14 to 32 weeks of gestation. Furthermore, integration and transition were observed between vimentin-positive portal myofibroblasts (pMFs) and ductal plate cells or bile ducts. In serial section of the developing human liver (9-32 weeks), we observed that ductal plate or bile ducts cells co-expressed vimentin and CK19. Conclusion Our findings show the presence of mesenchymal-epithelial transition during the development of ductal plate in human liver, which is associated with the formation of bile ducts.
Key words:  hepatic stem cells  developing human liver  ductal plate  epithelial mesenchymal transition  immunohistochemistry