Tan C E, Chan V S, Yong R Y, Vijayan V, Tan W L, Fook Chong S M, Ho J M, Cheng H H
Department of Pediatric Surgery, Singapore General Hospital, Singapore.
Pathol Int. 1995 Nov;45(11):815-24. doi: 10.1111/j.1440-1827.1995.tb03401.x.
Biliary atresia is an important cause of neonatal obstructive jaundice in which there is inflammation, sclerosis and eventual obliteration of the bile duct system. Its onset may be antenatal, affecting the normal development of the biliary system. The intrahepatic biliary system is derived from the ductal plate, a sheath of cuboidal epithelium that appears at the hepatocyte-mesenchymal junction around the portal vein branches at 6 weeks gestation. This epithelial structure is moulded into a network of tubular bile ducts by the proliferating mesenchyme. Certain portions of the ductal plate are selected to become definitive bile ducts, while redundant biliary epithelium is deleted. The molecular dynamics controlling the intra-uterine development of the biliary system in humans are not yet clearly understood. Transforming growth factor-beta 1 is a cytokine that stimulates mesenchymal proliferation and inhibits epithelial growth, and has been shown to be important in organogenesis. In the present study, the pattern of TGF beta 1 peptide immunolocalization was investigated with the aid of computerized image analysis, in normal human bile duct development and in biliary atresia. TGF beta 1 peptide was detected within hepatocytes and ductal plate epithelium from 7 weeks gestation; increased TGF beta 1 immunoreactivity was present within the epithelium of developing bile ducts at 13 weeks gestation, and apical polarization of the cytokine was observed from 16 weeks gestation. In biliary atresia, the TGF beta 1 immunoreactivity pattern within the bile duct structures at the porta hepatis and within intrahepatic portal tracts resembled that of the primitive ductal plate, and there was no significant apical polarization. This may indicate a developmental arrest in the normal ductal plate remodelling process in biliary atresia, and suggests an underlying epithelial-mesenchymal interactive disorder.
胆道闭锁是新生儿梗阻性黄疸的一个重要病因，其特征为胆管系统出现炎症、硬化并最终闭塞。其发病可能在产前，影响胆道系统的正常发育。肝内胆管系统源自导管板，这是一层立方上皮细胞鞘，在妊娠6周时出现在门静脉分支周围的肝细胞-间充质交界处。这个上皮结构通过增殖的间充质被塑造成管状胆管网络。导管板的某些部分被选择成为永久性胆管，而多余的胆管上皮则被清除。目前尚不清楚控制人类胆道系统子宫内发育的分子动力学。转化生长因子-β1是一种刺激间充质增殖并抑制上皮生长的细胞因子，已被证明在器官发生中起重要作用。在本研究中，借助计算机图像分析，研究了转化生长因子-β1肽在正常人类胆管发育和胆道闭锁中的免疫定位模式。从妊娠7周起，在肝细胞和导管板上皮内检测到转化生长因子-β1肽；在妊娠13周时，发育中胆管的上皮内转化生长因子-β1免疫反应性增加，从妊娠16周起观察到该细胞因子的顶端极化。在胆道闭锁中，肝门部胆管结构和肝内门静脉周围的转化生长因子-β1免疫反应性模式类似于原始导管板，且无明显的顶端极化。这可能表明胆道闭锁中正常导管板重塑过程的发育停滞，并提示存在潜在的上皮-间充质相互作用紊乱。
