Estrogens and the pathophysiology of the biliary tree
Estrogens and the pathophysiology of the biliary tree
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DOI：
10.3748/wjg.v12.i22.3537
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发表时间：
2006-06-14
影响因子：
4.3
通讯作者：
Gaudio, Eugenio
中科院分区：
文献类型：
--
作者：
Alvaro, Domenico;Mancino, Maria Grazia;Gaudio, Eugenio
在过去的几十年里，当雌激素受体（ER）亚型被鉴定出来时，关于雌激素对不同组织作用的科学框架已经得到了极大的扩展。雌激素不仅对女性生殖系统至关重要，而且还控制其他组织的基本功能，包括心血管系统，骨骼，大脑和肝脏。最近，雌激素已被证明靶向胆管树，在那里它们调节胆管细胞（胆管衬里的上皮细胞）的增殖和分泌活动。通过作用于雌激素受体（ER-α）和（ER-β）亚型，并通过激活基因组或非基因组途径，雌激素在生长因子和细胞因子的复杂循环中发挥关键作用，调节胆管细胞对损伤的增殖反应。具体地，雌激素激活细胞内信号级联[ERK 1/2（细胞外调节激酶1/2，PI 3-激酶/AKT（磷脂酰肌醇-3 '激酶/AKT）]，其是生长因子如胰岛素样生长因子（IGF 1）、神经生长因子（NGF）和血管内皮生长因子（VEGF）的典型信号，从而增强其作用。此外，雌激素刺激增殖的胆管细胞分泌不同的生长因子。本文综述了雌激素在正常和病理状态下对胆管细胞功能的调节作用及其机制的最新研究进展。(C)2006年，WJG出版社。All rights reserved.
The scientific framework concerning estrogen effects on different tissues has expanded enormously during the last decades, when estrogen receptor (ER) subtypes were identified. Estrogens are not only essential for the female reproductive system, but they also control fundamental functions in other tissues including the cardiovascular system, bone, brain and liver. Recently, estrogens have been shown to target the biliary tree, where they modulate the proliferative and secretory activities of cholangiocytes, the epithelial cells lining bile ducts. By acting on both estrogen receptors (ER-alpha) and (ER-beta) subtypes, and by activating either genomic or non-genomic pathways, estrogens play a key role in the complex loop of growth factors and cytokines, which modulates the proliferative response of cholangiocytes to damage. Specifically, estrogens activate intracellular signalling cascades [ERK1/2 (extracellular regulated kinases 1/2, PI3- kinase/AKT (phosphatidylinositol-3' kinase/AKT)] typical of growth factors such as insulin like growth factor (IGF1), nerve growth factor (NGF) and vascular endothelial growth factor (VEGF), thus potentiating their action. In addition, estrogens stimulate the secretion of different growth factors in proliferating cholangiocytes. This review specifically deals with the recent advances related to the role and mechanisms by which estrogens modulate cholangiocyte functions in normal and pathological conditions. (C) 2006 The WJG Press. All rights reserved.