Division of Gastroenterology, Children's Hospital Boston, Harvard Medical School, Boston, Massachusetts, USA.
Prog Mol Biol Transl Sci. 2010;96:207-29. doi: 10.1016/B978-0-12-381280-3.00009-9.
Regulation of gene expression within the intestinal epithelium is complex and controlled by various signaling pathways that regulate the balance between proliferation and differentiation. Proliferation is required both to grow and to replace cells lost through apoptosis and attrition, yet in all but a few cells, differentiation must take place to prevent uncontrolled growth (cancer) and to provide essential functions. In this chapter, we review the major signaling pathways underlying regulation of gene expression within the intestinal epithelium, based primarily on data from mouse models, as well as specific morphogens and transcription factor families that have a major role in regulating intestinal gene expression, including the Hedgehog family, Forkhead Box (FOX) factors, Homeobox (HOX) genes, ParaHox genes, GATA transcription factors, canonical Wnt/β-catenin signaling, EPH/Ephrins, Sox9, BMP signaling, PTEN/PI3K, LKB1, K-RAS, Notch pathway, HNF, and MATH1. We also briefly highlight important emerging areas of gene regulation, including microRNA (miRNA) and epigenetic regulation.
肠道上皮细胞中的基因表达调控非常复杂,受多种信号通路的调控,这些信号通路调节增殖和分化之间的平衡。增殖不仅是生长所必需的,也是为了替换通过细胞凋亡和磨损而损失的细胞,但除了少数细胞外,分化必须发生以防止不受控制的生长(癌症)并提供必要的功能。在本章中,我们主要基于来自小鼠模型的数据,以及在调节肠道基因表达方面具有主要作用的特定形态发生素和转录因子家族,综述肠道上皮细胞中基因表达调控的主要信号通路,包括 Hedgehog 家族、Forkhead Box (FOX) 因子、Homeobox (HOX) 基因、ParaHox 基因、GATA 转录因子、经典 Wnt/β-catenin 信号、EPH/Ephrins、Sox9、BMP 信号、PTEN/PI3K、LKB1、K-RAS、Notch 通路、HNF 和 MATH1。我们还简要介绍了基因调控的一些新出现的重要领域,包括 microRNA (miRNA) 和表观遗传调控。