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Epigenetic Mechanisms of Pancreatobiliary Fibrosis

  • Pancreas (V Chandrasekhara, Section Editor)
  • Published:
Current Treatment Options in Gastroenterology Aims and scope Submit manuscript

Abstract

Purpose of review

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.

Recent findings

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.

Summary

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.

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Acknowledgments

The authors acknowledge Lyndsay M. Busby for her secretarial support.

Funding

This work was supported by grants DK100575, DK113339, DK117861 and from the National Institutes of Health.

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Authors and Affiliations

  1. Division of Gastroenterology and Hepatology, Rochester, FL, USA

    Sayed Obaidullah Aseem & Robert C. Huebert

  2. Gastroenterology Research Unit, Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA

    Sayed Obaidullah Aseem & Robert C. Huebert

  3. Mayo Clinic Foundation, Rochester, MN, USA

    Robert C. Huebert

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Correspondence to Robert C. Huebert.

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Aseem, S.O., Huebert, R.C. Epigenetic Mechanisms of Pancreatobiliary Fibrosis. Curr Treat Options Gastro 17, 342–356 (2019). https://doi.org/10.1007/s11938-019-00239-0

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