The Hippo pathway in intestinal regeneration and disease.
The Hippo pathway in intestinal regeneration and disease.
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DOI：
10.1038/nrgastro.2016.59
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发表时间：
2016-06
期刊：
影响因子：
--
通讯作者：
Guan KL
中科院分区：
文献类型：
--
作者：
Hong AW;Meng Z;Guan KL
Hippo途径是从黑腹果蝇到哺乳动物保守的信号级联反应。哺乳动物核心激酶组分包括MST 1和MST 2、SAV 1、LATS 1和LATS 2以及MOB1A和MOB1B。转录共激活因子YAP 1和TAZ是Hippo通路的下游效应子，调节靶基因的表达。Hippo信号传导在控制器官大小、组织稳态和再生中具有关键作用，并且Hippo通路的失调可导致不受控制的细胞生长和恶性转化。哺乳动物肠道由干细胞区室以及分化的细胞组成，并且其在损伤后快速再生的能力使其成为研究组织稳态、再生和肿瘤发生的优良模型系统。一些研究已经确定了Hippo途径在这些过程中的重要作用。此外，Hippo和其他信号通路之间的串扰提供了组织稳态的紧密但多功能的调节。在这篇综述中，我们总结了肠道中Hippo通路在这些生理过程中的作用及其相关机制的研究，并讨论了未来的研究方向和潜在的治疗策略，靶向Hippo信号在肠道疾病中的作用。
The Hippo pathway is a signalling cascade conserved from Drosophila melanogaster to mammals. The mammalian core kinase components comprise MST1 and MST2, SAV1, LATS1 and LATS2 and MOB1A and MOB1B. The transcriptional co-activators YAP1 and TAZ are the downstream effectors of the Hippo pathway and regulate target gene expression. Hippo signalling has crucial roles in the control of organ size, tissue homeostasis and regeneration, and dysregulation of the Hippo pathway can lead to uncontrolled cell growth and malignant transformation. Mammalian intestine consists of a stem cell compartment as well as differentiated cells, and its ability to regenerate rapidly after injury makes it an excellent model system to study tissue homeostasis, regeneration and tumorigenesis. Several studies have established the important role of the Hippo pathway in these processes. In addition, crosstalk between Hippo and other signalling pathways provides tight, yet versatile, regulation of tissue homeostasis. In this Review, we summarize studies on the role of the Hippo pathway in the intestine on these physiological processes and the underlying mechanisms responsible, and discuss future research directions and potential therapeutic strategies targeting Hippo signalling in intestinal disease.
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