Targeting of miR-93-5p/Mfn2 Axis Attenuates Lung Fibrosis in Rats With Acute Respiratory Distress Syndrome by Regulating Endoplasmic Reticulum Stress.

Summary

In an LPS-induced ARDS rat model, miR-93-5p was upregulated and inversely correlated with Mfn2. Systemic inhibition of miR-93-5p increased Mfn2, reduced ER stress and inflammation, and diminished collagen deposition, thereby attenuating ARDS-associated pulmonary fibrosis.

Key Findings

• miR-93-5p is significantly upregulated in lungs of LPS-induced ARDS rats and negatively correlates with Mfn2 expression.
• Antagomir-mediated inhibition of miR-93-5p increases Mfn2, attenuates ER stress and inflammation, and reduces collagen deposition.
• Targeting miR-93-5p/Mfn2 ameliorates ARDS-associated pulmonary fibrosis in vivo.

Clinical Implications

While preclinical, targeting miR-93-5p/Mfn2 and ER stress may inspire translational anti-fibrotic therapies to improve long-term outcomes in ARDS survivors.

Limitations

• Single animal model limits generalizability; human validation is lacking
• Potential off-target effects of antagomir and absence of long-term functional outcomes

Future Directions

Validate the miR-93-5p/Mfn2 axis in human ARDS tissues and test targeted modulators in large-animal models with pulmonary function endpoints.