Pro-inflammatory and pro-fibrotic role of long non-coding RNA RMRP in pediatric asthma through targeting...

Area of Science:

• Pulmonary Medicine
• Molecular Biology
• Immunology

Background:

• Pediatric asthma is a prevalent inflammatory pulmonary condition.
• Long noncoding RNAs (lncRNAs) are increasingly recognized for their roles in disease pathogenesis.
• The specific role of RMRP in pediatric asthma requires further elucidation.

Purpose of the Study:

• To investigate the role of RMRP in a mouse model of ovalbumin (OVA)-induced asthma.
• To explore the regulatory relationship between RMRP, miR-206, and CCL2 in asthma.
• To assess the impact of RMRP on the TGF-β/Smad2 signaling pathway in airway smooth muscle cells.

Main Methods:

• Ovalbumin (OVA) sensitization was used to induce asthma in an 8-week-old mouse model.
• Quantitative PCR (qPCR) was employed to evaluate RMRP, miR-206, and CCL2 expression in pulmonary tissues.
• Enzyme-linked immunosorbent assay (ELISA) was used to measure IL-4, IL-5, and IL-13 cytokine levels in bronchoalveolar lavage fluid.
• RMRP overexpression and TGF-β/Smad2 pathway blockade were performed in human airway smooth muscle cells (ASMCs).

Main Results:

• OVA-induced asthmatic mice exhibited elevated RMRP and CCL2 expression, alongside reduced miR-206 levels.
• Overexpression of RMRP in ASMCs led to increased asthma biomarker levels.
• RMRP acted as a molecular sponge for miR-206, consequently upregulating CCL2 expression.
• Blocking the TGF-β/Smad2 pathway in RMRP-overexpressing ASMCs reduced inflammatory cytokines and cell viability while promoting apoptosis.

Conclusions:

• The RMRP/miR-206/CCL2 regulatory axis plays a significant role in the pathogenesis of pediatric asthma.
• RMRP contributes to asthma development by modulating miR-206 and CCL2 expression.
• Targeting the TGF-β/Smad2 pathway may offer a therapeutic strategy for RMRP-mediated asthma.