MicroRNA-30d/JAG1 axis modulates pulmonary fibrosis through Notch signaling pathway

Area of Science:

• Pulmonary Medicine
• Molecular Biology
• Cell Biology

Background:

• Pulmonary fibrosis (PF) is a progressive lung disease characterized by excessive fibroblast activity and extracellular matrix deposition, often leading to fatal respiratory failure.
• The JAG1/Notch signaling pathway is implicated in fibrotic processes, including PF, but its precise regulatory mechanisms require further elucidation.

Purpose of the Study:

• To investigate the role of JAG1 and its regulation by microRNA-30d (miR-30d) in the pathogenesis of pulmonary fibrosis.
• To explore the potential of targeting the miR-30d/JAG1 axis as a therapeutic strategy for PF.

Main Methods:

• Analysis of JAG1 mRNA and protein expression in PF tissues.
• In vitro studies using primary normal human lung fibroblasts (NHLF) treated with TGF-β1.
• Manipulation of JAG1 and miR-30d expression using knockdown and overexpression techniques.
• Assessment of fibroblast proliferation, α-SMA, and Collagen I levels.
• Luciferase reporter assays to confirm direct binding of miR-30d to JAG1 3'-UTR.

Main Results:

• JAG1 expression was upregulated in PF tissues and promoted by TGF-β1.
• miR-30d expression was downregulated in PF tissues.
• Overexpression of miR-30d inhibited TGF-β1-induced NHLF proliferation, α-SMA, and Collagen I production.
• miR-30d directly targeted JAG1, suppressing its expression and activity.
• JAG1 overexpression partially reversed the antifibrotic effects of miR-30d.

Conclusions:

• miR-30d acts as a tumor suppressor in PF by inhibiting the JAG1/Notch signaling pathway.
• Restoring miR-30d levels can attenuate fibroblast activation and extracellular matrix production in response to TGF-β1.
• The miR-30d/JAG1 axis represents a promising therapeutic target for pulmonary fibrosis.