Role of G protein-coupled receptors-microRNA interactions in gastrointestinal pathophysiology

Am J Physiol Gastrointest Liver Physiol. 2017 Nov 1;313(5):G361-G372. doi: 10.1152/ajpgi.00144.2017. Epub 2017 Aug 3.

Abstract

G protein-coupled receptors (GPCRs) make up the largest transmembrane receptor superfamily in the human genome and are expressed in nearly all gastrointestinal cell types. Coupling of GPCRs and their respective ligands activates various phosphotransferases in the cytoplasm, and, thus, activation of GPCR signaling in intestine regulates many cellular and physiological processes. Studies in microRNAs (miRNAs) demonstrate that they represent critical epigenetic regulators of different pathophysiological responses in different organs and cell types in humans and animals. Here, we reviewed recent research on GPCR-miRNA interactions related to gastrointestinal pathophysiology, such as inflammatory bowel diseases, irritable bowel syndrome, and gastrointestinal cancers. Given that the presence of different types of cells in the gastrointestinal tract suggests the importance of cell-cell interactions in maintaining gastrointestinal homeostasis, we also discuss how GPCR-miRNA interactions regulate gene expression at the cellular level and subsequently modulate gastrointestinal pathophysiology through molecular regulatory circuits and cell-cell interactions. These studies helped identify novel molecular pathways leading to the discovery of potential biomarkers for gastrointestinal diseases.

Keywords: epigenetics; inflammation; inflammatory bowel disease; intestinal epithelial cells; microribonucleic acid; neuropeptides.

Publication types

  • Review

MeSH terms

  • Cell Communication / physiology
  • Epigenesis, Genetic / physiology
  • Gastrointestinal Diseases* / genetics
  • Gastrointestinal Diseases* / physiopathology
  • Gastrointestinal Tract / physiology
  • Gastrointestinal Tract / physiopathology
  • Gene Expression
  • Humans
  • MicroRNAs / genetics*
  • Receptors, G-Protein-Coupled / physiology*
  • Receptors, Interleukin-6 / genetics
  • Receptors, Neurokinin-3 / genetics
  • Signal Transduction / physiology

Substances

  • MIRN221 microRNA, human
  • MicroRNAs
  • Receptors, G-Protein-Coupled
  • Receptors, Interleukin-6
  • Receptors, Neurokinin-3
  • TACR3 protein, human