mmu-microRNA-92a-3p attenuates pulmonary fibrosis by modulating Cpeb4-mediated Smad2/3 signaling pathway

Area of Science:

• Biomedical research
• Molecular biology
• Pulmonary medicine

Background:

• Pulmonary fibrosis (PF) is a chronic lung disease with unclear molecular mechanisms.
• The role of microRNA (miR)-92a-3p in PF pathogenesis requires further elucidation.

Purpose of the Study:

• To investigate the mechanism of mmu-miR-92a-3p in pulmonary fibrosis (PF).
• To explore the role of the cytoplasmic polyadenylation element-binding protein 4 (Cpeb4)/Smad2/3 axis in PF.
• To determine if mmu-miR-92a-3p modulates PF via the Cpeb4/Smad2/3 pathway.

Main Methods:

• Pulmonary fibrosis was induced in mice using bleomycin (BLM).
• Adenovirus vectors were used to modulate mmu-miR-92a-3p and Cpeb4 expression in BLM-treated mice.
• Expression levels of mmu-miR-92a-3p, Cpeb4, and Smad2/3 were analyzed in lung tissues.
• Alveolar cell apoptosis, collagen deposition, and serum inflammatory factors were assessed.
• The interaction between mmu-miR-92a-3p and Cpeb4 was investigated.

Main Results:

• BLM-induced PF mice showed decreased mmu-miR-92a-3p and increased Cpeb4 and Smad2/3 expression.
• PF mice exhibited elevated inflammation, apoptosis, and collagen deposition.
• Upregulating mmu-miR-92a-3p or downregulating Cpeb4 attenuated PF symptoms.
• mmu-miR-92a-3p was found to directly target Cpeb4.
• Modulating mmu-miR-92a-3p or Cpeb4 inactivated the Smad2/3 signaling pathway.

Conclusions:

• mmu-miR-92a-3p plays a protective role in pulmonary fibrosis.
• The mechanism involves mmu-miR-92a-3p targeting Cpeb4 and subsequently inhibiting the Smad2/3 signaling pathway.
• This study provides a novel molecular mechanism for pulmonary fibrosis and suggests potential therapeutic targets.