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Mechanism of miR-130b-3p in relieving airway inflammation in asthma through HMGB1-TLR4-DRP1 axis

Xue Han1,2, Yilan Song1,3, Yihua Piao1,4

  • 1Jilin Key Laboratory for Immune and Targeting Research on Common Allergic Diseases, Yanbian University, Yanji, 133002, People's Republic of China.

Cellular and Molecular Life Sciences : CMLS
|December 20, 2024
PubMed

Insights

MicroRNA miR-130b-3p reduces asthma severity by targeting HMGB1, thereby inhibiting the HMGB1/TLR4/DRP1 pathway. This finding offers a potential new treatment for asthma.

Area of Science:

  • Immunology
  • Molecular Biology
  • Respiratory Medicine

Background:

  • Asthma is a chronic respiratory disease involving airway inflammation and hypersensitivity.
  • MicroRNAs (miRNAs) play a role in asthma pathogenesis, but the specific function of miR-130b-3p is unclear.

Purpose of the Study:

  • To investigate if miR-130b-3p can alleviate house dust mite (HDM)-induced asthma.
  • To explore the role of the High-mobility group box protein 1 (HMGB1)/Toll-like receptor 4 (TLR4)/mitochondrial fission protein (DRP1) signaling pathway in this process.

Main Methods:

  • Studied the interaction between miR-130b-3p and HMGB1 mRNA.
  • Administered miR-130b-3p agomir or used HMGB1 conditional knockout (CKO) in HDM-induced asthma mouse models.
  • Analyzed airway inflammation, hyperresponsiveness, Th2 cytokines in bronchoalveolar lavage fluid (BALF) and lymph nodes.
  • Utilized flow cytometry to assess Th2 inflammation in specific lung cells.

Main Results:

  • miR-130b-3p directly targets HMGB1, reducing its mRNA and protein levels and nuclear-cytoplasmic translocation.
  • Both miR-130b-3p agomir and HMGB1 CKO significantly reduced airway inflammation and hyperresponsiveness in asthmatic mice.
  • Th2-type cytokines were decreased in BALF and lymph nodes of treated mice.
  • HMGB1 CKO helped alleviate Th2 inflammation in specific lung cells.

Conclusions:

  • miR-130b-3p acts as a key regulator in asthma, exerting anti-inflammatory effects.
  • The mechanism involves targeting HMGB1 and subsequently inhibiting the HMGB1/TLR4/DRP1 signaling axis.
  • This research identifies miR-130b-3p as a promising therapeutic target for asthma management.
Keywords:
AsthmaHMGB1MiR-130b-3p

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