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LncRNA AK089514/miR-125b-5p/TRAF6 axis mediates macrophage polarization in allergic asthma
Xiaolong Zhu1,2,3,4, Ling He1,2,3,5, Xueqin Li1,2,3
1Central Laboratory, The First Affiliated Hospital of Wannan Medical College (Yijishan Hospital of Wannan Medical College), 2 Zheshan Western Road, Wuhu, 241001, People's Republic of China.
Background:
Micro RNA (miRNA) plays important roles in macrophage polarization. However, the manner in which miRNA regulate macrophage polarization in response to dermatophagoides farinae protein 1(Der f1)-induced asthma has not been defined. This study aims to explore the role of miRNAs in regulating macrophages in asthma.
Methods:
The microRNAs which may regulate asthma were selectd by Microarrays. The function of miR-125b-5p in macrophage and Der f1-induced asthma were detected in vivo experiment. The long non coding RNA (lncRNA) AK089514/miR-125b-5p/TRAF6 axis was predicted by bioinformatics and confirmed by dual luciferase reporter assay.
Results:
In this study, we found that miR-125b-5p is highly expressed in M2 macrophages and bronchoalveolar lavage fluid (BALF) cells with Der f1-induced asthma. In response to the challenge of Der f1, miR-125b-5p KD attenuated allergic airway inflammation of mice by preventing M2 macrophages polarization. Mechanistic studies indicated that lncRNA AK089514 functioned as a competing endogenous RNA for miR-125b-5p, thereby leading to the depression of its endogenous target TNF receptor associated factor 6 (TRAF6).
Conclusions:
miR-125b-5p is significantly over-expressed in asthma, and AK089514-miR-125b-5p-TRAF6 axis play critical role in asthma by modulating macrophage polarization. Our findings may provide a potential new target for potential therapeutic and diagnostic target in asthma.
Insights
MicroRNA-125b-5p is highly expressed in asthma and regulates macrophage polarization. Targeting the AK089514-miR-125b-5p-TRAF6 axis may offer new therapeutic strategies for allergic airway inflammation.
Area of Science:
- Immunology
- Molecular Biology
- Respiratory Medicine
Background:
- MicroRNAs (miRNAs) are crucial regulators of macrophage polarization.
- The specific role of miRNAs in macrophage polarization during Dermatophagoides farinae protein 1 (Der f1)-induced asthma remains unclear.
Purpose of the Study:
- To investigate the function of miRNAs in regulating macrophages within the context of Der f1-induced asthma.
- To elucidate the molecular mechanisms underlying miRNA-mediated macrophage polarization in asthma.
Main Methods:
- Microarrays were employed to identify potential asthma-related microRNAs.
- In vivo experiments assessed the function of miR-125b-5p in macrophages and Der f1-induced asthma models.
- Bioinformatics and dual-luciferase reporter assays confirmed the lncRNA AK089514/miR-125b-5p/TRAF6 regulatory axis.
Main Results:
- miR-125b-5p was found to be highly expressed in M2 macrophages and bronchoalveolar lavage fluid (BALF) cells from mice with Der f1-induced asthma.
- Knockdown of miR-125b-5p (KD) alleviated allergic airway inflammation by inhibiting M2 macrophage polarization.
- lncRNA AK089514 acts as a competing endogenous RNA (ceRNA) for miR-125b-5p, downregulating its target, TNF receptor associated factor 6 (TRAF6).
Conclusions:
- miR-125b-5p is significantly overexpressed in asthma.
- The AK089514-miR-125b-5p-TRAF6 axis plays a critical role in asthma pathogenesis by modulating macrophage polarization.
- This axis represents a potential therapeutic and diagnostic target for asthma.
