1. Academic Validation
  2. MiR-124a Mediates the Impairment of Intestinal Epithelial Integrity by Targeting Aryl Hydrocarbon Receptor in Crohn's Disease

MiR-124a Mediates the Impairment of Intestinal Epithelial Integrity by Targeting Aryl Hydrocarbon Receptor in Crohn's Disease

  • Inflammation. 2020 Oct;43(5):1862-1875. doi: 10.1007/s10753-020-01259-0.
Xiaojing Zhao  # 1 Jiajia Li  # 1 Jingjing Ma 1 Chunhua Jiao 1 Xinyun Qiu 1 Xiufang Cui 1 Di Wang 1 Hongjie Zhang 2
Affiliations

Affiliations

  • 1 Department of Gastroenterology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, Jiangsu, China.
  • 2 Department of Gastroenterology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, Jiangsu, China. hjzhang06@163.com.
  • # Contributed equally.
Abstract

Growing evidence suggested that MicroRNAs (miRNAs) contributed to the progression of Crohn's disease (CD), but the exact physiological functions of many miRNAs in CD patients still remain illusive. In this study, we explore the potent pathogenicity of miRNAs in CD. Expressions of miRNAs and Aryl Hydrocarbon Receptor (AHR) protein were determined in the colitic colon of 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced colitis mice and CD patients. Colitis was induced in wild-type (WT), miR-124a overexpression (miR-124a-Nju), and AHR knockout (AHR-/-) mice. Intestinal barrier function was evaluated in colitis mice and Caco2 monolayers. There was a negative relationship between miR-124a and AHR protein in inflamed colons from CD patients. MiR-124a-Nju and AHR-/- mice treated with TNBS had more severe intestinal inflammation than WT mice. Both miR-124a-Nju mice and AHR-/- mice underwent evident intestinal barrier destruction, and anti-miR-124a administration could reverse this dysfunction in miR-124a-Nju mice but not in AHR-/- mice. In vitro studies revealed that miR-124a mimics downregulated the expression of AHR and tight junction proteins and induced hyperpermeability by increasing miR-124a expression, which was abrogated by miR-124a inhibitor and AHR antagonist FICZ. This study suggests that miR-124a can induce intestinal inflammation and cause intestinal barrier dysfunction by supressing AHR.

Keywords

Crohn’s disease; aryl hydrocarbon receptor; intestinal barrier dysfunction; miR-124a.

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