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刺猬信号通路作为肝纤维化的关键因素:新见解与展望

Hedgehog signaling pathway as key player in liver fibrosis: new insights and perspectives.

作者信息

Yang Jing-Jing, Tao Hui, Li Jun

机构信息

The Second Hospital of Anhui Medical University, Department of Pharmacology , Hefei 230601 , China.

出版信息

Expert Opin Ther Targets. 2014 Sep;18(9):1011-21. doi: 10.1517/14728222.2014.927443. Epub 2014 Jun 17.

Abstract

INTRODUCTION

Activation of hepatic stellate cells (HSCs) is a pivotal cellular event in liver fibrosis. Therefore, improving our understanding of the molecular pathways that are involved in these processes is essential to generate new therapies for liver fibrosis. Greater knowledge of the role of the hedgehog signaling pathway in liver fibrosis could improve understanding of the liver fibrosis pathogenesis.

AREAS COVERED

The aim of this review is to describe the present knowledge about the hedgehog signaling pathway, which significantly participates in liver fibrosis and HSC activation, and look ahead on new perspectives of hedgehog signaling pathway research. Moreover, we will discuss the different interactions with hedgehog signaling pathway-regulated liver fibrosis.

EXPERT OPINION

The hedgehog pathway modulates several important aspects of function, including cell proliferation, activation and differentiation. Targeting the hedgehog pathway can be a promising direction in liver fibrosis treatment. We discuss new perspectives of hedgehog signaling pathway activation in liver fibrosis and HSC fate, including DNA methylation, methyl CpG binding protein 2, microRNA, irradiation and metabolism that influence hedgehog signaling pathway transduction. These findings identify the hedgehog pathway as a potentially important for biomarker development and therapeutic targets in liver fibrosis. Future studies are needed in order to find safer and more effective hedgehog-based drugs.

摘要

引言

肝星状细胞(HSCs)的激活是肝纤维化过程中的关键细胞事件。因此,深入了解参与这些过程的分子途径对于开发新的肝纤维化治疗方法至关重要。更多地了解刺猬信号通路在肝纤维化中的作用有助于增进对肝纤维化发病机制的理解。

涵盖领域

本综述旨在描述目前关于刺猬信号通路的知识,该通路在肝纤维化和HSC激活中发挥着重要作用,并展望刺猬信号通路研究的新前景。此外,我们将讨论与刺猬信号通路调控的肝纤维化相关的不同相互作用。

专家观点

刺猬信号通路调节功能的几个重要方面,包括细胞增殖、激活和分化。靶向刺猬信号通路可能是肝纤维化治疗的一个有前景的方向。我们讨论了肝纤维化和HSC命运中刺猬信号通路激活的新前景,包括影响刺猬信号通路转导的DNA甲基化、甲基CpG结合蛋白2、微小RNA、辐射和代谢。这些发现表明刺猬信号通路在肝纤维化生物标志物开发和治疗靶点方面可能具有重要意义。未来需要开展研究以找到更安全、更有效的基于刺猬信号通路的药物。

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