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MicroRNA-124 Promotes Intestinal Inflammation by Targeting Aryl Hydrocarbon Receptor in Crohn's Disease

Ye Zhao1, Teng Ma2, Weixu Chen3

  • 1Department of Gastroenterology, Zhongda Hospital, Southeast University, Nanjing, Jiangsu Province, PR China Department of Gastroenterology, the First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, PR China.

Journal of Crohn'S & Colitis
|January 24, 2016
PubMed
Abstract

Insights

MicroRNA-124 (miR-124) promotes intestinal inflammation in Crohn's disease (CD) by inhibiting the aryl hydrocarbon receptor (AHR). This study reveals miR-124 as a key player in CD pathogenesis.

Area of Science:

  • Gastroenterology
  • Molecular Biology
  • Immunology

Background:

  • MicroRNA (miRNA) dysregulation is implicated in Crohn's disease (CD) pathogenesis.
  • The specific roles and targets of miRNAs in CD remain largely uncharacterized.
  • This study focuses on aberrant colonic mucosal miRNAs in active CD patients.

Purpose of the Study:

  • To investigate the role of microRNA-124 (miR-124) in the colonic mucosa of active Crohn's disease (CD) patients.
  • To determine the relationship between miR-124 and its target, aryl hydrocarbon receptor (AHR).
  • To elucidate the functional impact of miR-124 on intestinal inflammation and CD pathogenesis.

Main Methods:

  • Quantitative real-time polymerase chain reaction (PCR) to assay miRNA levels in inflamed colon tissue.
  • Investigation of miR-124 and AHR interaction in intestinal epithelial cells (IECs) and a mouse model of colitis.
  • In vivo studies using miR-124 inhibitors and precursors in experimental colitis models.

Main Results:

  • An inverse correlation was observed between miR-124 and AHR protein levels in active CD patients.
  • miR-124 directly targets the AHR 3'-untranslated region (3'-UTR), suppressing AHR expression in intestinal cells.
  • Modulation of miR-124 levels in experimental colitis significantly altered disease severity, indicating its regulatory role in inflammation.

Conclusions:

  • miR-124 inhibition of AHR contributes to intestinal inflammation by affecting pro-inflammatory cytokine production.
  • This miR-124/AHR axis plays a crucial role in promoting the pathogenesis of Crohn's disease.
  • miR-124 represents a potential therapeutic target for managing CD-associated intestinal inflammation.
Keywords:
Crohn’s diseasearyl hydrocarbon receptorintestinal epithelial cellmiR-124

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