Aseem Sayed Obaidullah, Huebert Robert C
Division of Gastroenterology and Hepatology, Rochester, FL, USA.
Gastroenterology Research Unit, Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA.
Curr Treat Options Gastroenterol. 2019 Sep;17(3):342-356. doi: 10.1007/s11938-019-00239-0.
The goal of this manuscript is to review the current literature related to fibrogenesis in the pancreatobiliary system and how this process contributes to pancreatic and biliary diseases. In particular, we seek to define the current state of knowledge regarding the epigenetic mechanisms that govern and regulate tissue fibrosis in these organs. A better understanding of these underlying molecular events will set the stage for future epigenetic therapeutics.
We highlight the significant advances that have been made in defining the pathogenesis of pancreatobiliary fibrosis as it relates to chronic pancreatitis, pancreatic cancer, and the fibro-obliterative cholangiopathies. We also review the cell types involved as well as concepts related to epithelial-mesenchymal crosstalk. Furthermore, we outline important signaling pathways (e.g., TGFβ) and diverse epigenetic processes (i.e., DNA methylation, non-coding RNAs, histone modifications, and 3D chromatin remodeling) that regulate fibrogenic gene networks in these conditions. We review a growing body of scientific evidence linking epigenetic regulatory events to fibrotic disease states in the pancreas and biliary system. Advances in this understudied area will be critical toward developing epigenetic pharmacological approaches that may lead to more effective treatments for these devastating and difficult to treat disorders.
本手稿的目的是回顾与胰胆系统纤维化形成相关的当前文献，以及该过程如何导致胰腺和胆道疾病。特别是，我们试图明确关于调控这些器官组织纤维化的表观遗传机制的当前知识状态。更好地理解这些潜在的分子事件将为未来的表观遗传治疗奠定基础。
我们强调在确定与慢性胰腺炎、胰腺癌和纤维闭塞性胆管病相关的胰胆纤维化发病机制方面取得的重大进展。我们还回顾了涉及的细胞类型以及与上皮-间质相互作用相关的概念。此外，我们概述了在这些情况下调节纤维化基因网络的重要信号通路（如TGFβ）和多种表观遗传过程（即DNA甲基化、非编码RNA、组蛋白修饰和三维染色质重塑）。我们回顾了越来越多将表观遗传调控事件与胰腺和胆道系统纤维化疾病状态联系起来的科学证据。在这个研究不足的领域取得进展对于开发可能导致对这些毁灭性且难以治疗的疾病更有效治疗方法的表观遗传药理学方法至关重要。
