Role of HCA2 in Regulating Intestinal Homeostasis and Suppressing Colon Carcinogenesis

Front Immunol. 2021 Feb 23:12:606384. doi: 10.3389/fimmu.2021.606384. eCollection 2021.

Abstract

Hydroxycarboxylic acid receptor 2 (HCA2) is vital for sensing intermediates of metabolism, including β-hydroxybutyrate and butyrate. It also regulates profound anti-inflammatory effects in various tissues, indicating that HCA2 may serve as an essential therapeutic target for mediating inflammation-associated diseases. Butyrate and niacin, endogenous and exogenous ligands of HCA2, have been reported to play an essential role in maintaining intestinal homeostasis. HCA2, predominantly expressed in diverse immune cells, is also present in intestinal epithelial cells (IECs), where it regulates the intricate communication network between diet, microbiota, and immune cells. This review summarizes the physiological role of HCA2 in intestinal homeostasis and its pathological role in intestinal inflammation and cancer.

Keywords: HCA2; anti-inflammatory; colon cancer; intestinal homeostasis; intestinal inflammation; microbiota; mucosal immunity.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adenylyl Cyclases / genetics*
  • Adenylyl Cyclases / metabolism
  • Animals
  • Biomarkers
  • Carcinogenesis / genetics*
  • Carcinogenesis / immunology
  • Carcinogenesis / metabolism
  • Colonic Neoplasms / etiology*
  • Colonic Neoplasms / metabolism
  • Disease Susceptibility
  • Gene Expression Regulation
  • Homeostasis*
  • Humans
  • Intestinal Mucosa / immunology
  • Intestinal Mucosa / metabolism
  • Intestinal Mucosa / pathology
  • Intestines*
  • Metabolome
  • Microbiota
  • Signal Transduction

Substances

  • Biomarkers
  • ADCY10 protein, human
  • Adenylyl Cyclases