Circular RNA circSmad4 controls pulmonary fibrosis

Area of Science:

• Molecular Biology
• Pulmonary Medicine
• RNA Biology

Background:

• Pulmonary fibrosis is a progressive lung disease with limited therapies, characterized by fibroblast activation and extracellular matrix deposition.
• Circular RNAs (circRNAs) regulate gene expression, but their role in pulmonary fibrosis remains largely unknown.
• Investigating novel molecular targets is crucial for developing effective treatments for pulmonary fibrosis.

Purpose of the Study:

• To investigate the role of circSmad4 in pulmonary fibrosis.
• To explore the therapeutic potential of targeting circSmad4 in pulmonary fibrosis.

Main Methods:

• Utilized a bleomycin-induced pulmonary fibrosis mouse model.
• Employed small interfering RNA (siRNA) to silence circSmad4.
• Conducted in vitro experiments using TGF-β1-induced fibroblast activation models.
• Analyzed gene and protein expression, including fibrosis-related markers and cytokines.
• Investigated the miR-671-5p/Fgfr2 axis and used FGFR2-IN-1 for pharmacological inhibition.

Main Results:

• circSmad4 expression was significantly upregulated in pulmonary fibrosis models.
• Silencing circSmad4 alleviated lung fibrosis, reduced collagen deposition, and decreased inflammatory cytokine levels.
• circSmad4 promotes fibroblast activation by suppressing miR-671-5p and upregulating FGFR2 expression.
• si-circSmad4 treatment inhibited pro-fibrotic genes and extracellular matrix protein expression.
• Pharmacological inhibition of FGFR2 mimicked the anti-fibrotic effects of si-circSmad4.

Conclusions:

• circSmad4 acts as a key regulator in pulmonary fibrosis by modulating fibroblast activation, ECM deposition, and inflammation.
• Targeting circSmad4 presents a promising novel therapeutic strategy for pulmonary fibrosis.
• The circSmad4/miR-671-5p/Fgfr2 axis is a critical pathway in fibrotic lung disease progression.