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Epigenetic Regulation of Intestinal Fibrosis

  • Chao Li
  • John F. Kuemmerle
Chapter

Abstract

Genome-wide association studies have identified over 200 risk loci associated with Inflammatory Bowel Diseases (IBD), Crohn’s disease and Ulcerative colitis. These genetic factors, however, account for only a small proportion of genetic inheritability of disease. Our understanding of the pathogenesis of IBD has evolved and currently is thought to occur through the interaction between the host genome and their intestinal microbiome and metabolome with the innate and adaptive immune responses. Genetic risk alone, however, predicts only 25% of disease indicating that other factors including the intestinal environment can shape the epigenome and also independently confer heritable risk to patients. Epigenetic modifications regulate gene expression and protein production and play critical roles in shaping the intestinal immune response, mucosal homeostasis, and the wound-healing process. Analysis of the genetic risk in patients with Crohn’s disease combined with epigenetic marks reveals regulatory mechanisms that affect gene expression and disease phenotype. This chapter will focus on what is known about the alteration in the epigenome in Crohn’s disease and the mechanisms by which epigenetic risk factors determine development of fibrosis in Crohn’s disease. Studies of the epigenome have highlighted new therapeutic targets for therapeutic intervention of the development and progression of fibrosis.

Keywords

Fibrosis Epigenetics Inflammatory bowel diseases Mesenchymal cells Crohn’s disease 

Notes

Acknowledgments

Supported by DK49691 from NIH: National Institutes for Diabetes, Digestive and Kidney Diseases (JFK).

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Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of MedicineVirginia Commonwealth UniversityRichmondUSA
  2. 2.Department of Physiology and Biophysics, VCU Program in Enteric Neuromuscular Sciences, Medical College of Virginia CampusVirginia Commonwealth UniversityRichmondUSA

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