2. Academic Validation
  3. Epithelial microRNA-30a-3p targets RUNX2/HMGB1 axis to suppress airway eosinophilic inflammation in asthma

Epithelial microRNA-30a-3p targets RUNX2/HMGB1 axis to suppress airway eosinophilic inflammation in asthma

  • Respir Res. 2022 Jan 29;23(1):17. doi: 10.1186/s12931-022-01933-x.
Wenliang Wu 1 2,  Jiali Gao 1 2,  Dian Chen 1 2,  Gongqi Chen 1 2,  Yuchen Feng 1 2,  Chenli Chang 1 2,  Shengchong Chen 1 2,  Lingling Yi 3 4,  Guohua Zhen 5 6
Affiliations

Affiliations

  • 1 Division of Respiratory and Critical Care Medicine, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
  • 2 Key Laboratory of Respiratory Diseases, National Health Commission of People's Republic of China, and National Clinical Research Center for Respiratory Diseases, Wuhan, China.
  • 3 Division of Respiratory and Critical Care Medicine, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China. [email protected].
  • 4 Key Laboratory of Respiratory Diseases, National Health Commission of People's Republic of China, and National Clinical Research Center for Respiratory Diseases, Wuhan, China. [email protected].
  • 5 Division of Respiratory and Critical Care Medicine, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China. [email protected].
  • 6 Key Laboratory of Respiratory Diseases, National Health Commission of People's Republic of China, and National Clinical Research Center for Respiratory Diseases, Wuhan, China. [email protected].
PMID: 35093061 DOI: 10.1186/s12931-022-01933-x
Abstract

Background: Type 2-high asthma is a prominent endotype of asthma which is characterized by airway eosinophilic inflammation. Airway epithelial cells play a critical role in the pathogenesis of asthma. Our previous miRNA profiling data showed that miR-30a-3p was downregulated in bronchial epithelial cells from asthma patients. We hypothesize that epithelial miR-30a-3p plays a role in asthma airway inflammation.

Methods: We measured miR-30a-3p expression in bronchial brushings of asthma patients (n = 51) and healthy controls (n = 16), and analyzed the correlations between miR-30a-3p expression and airway eosinophilia. We examined whether Runt-related transcription factor 2 (RUNX2) was a target of miR-30a-3p and whether RUNX2 bound to the promoter of high mobility group box 1 (HMGB1) by using luciferase reporter assay and chromatin immunoprecipitation (ChIP)-PCR. The role of miR-30a-3p was also investigated in a murine model of allergic airway inflammation.

Results: We found that miR-30a-3p expression were significantly decreased in bronchial brushings of asthma patients compared to control subjects. Epithelial miR-30a-3p expression was negatively correlated with parameters reflecting airway eosinophilia including eosinophils in induced sputum and bronchial biopsies, and fraction of exhaled nitric oxide in asthma patients. We verified that RUNX2 is a target of miR-30a-3p. Furthermore, RUNX2 bound to the promoter of HMGB1 and upregulated HMGB1 expression. RUNX2 and HMGB1 expression was both enhanced in airway epithelium and was correlated with each other in asthma patients. Inhibition of miR-30a-3p enhanced RUNX2 and HMGB1 expression, and RUNX2 overexpression upregulated HMGB1 in BEAS-2B cells. Intriguingly, airway overexpression of mmu-miR-30a-3p suppressed Runx2 and Hmgb1 expression, and alleviated airway eosinophilia in a mouse model of allergic airway inflammation.

Conclusions: Epithelial miR-30a-3p could possibly target RUNX2/HMGB1 axis to suppress airway eosinophilia in asthma.

Keywords

Asthma; Eosinophilia; Epithelial cells; HMGB1; RUNX2; miR-30a-3p.

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