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

High mortality rates among patients with acute respiratory distress syndrome (ARDS) have been linked to pulmonary fibrosis. MicroRNAs exhibit significant potential in modulating pulmonary fibrosis. However, the specific role and underlying mechanisms of miR-93-5p in the context of ARDS-associated pulmonary fibrosis remain largely unexplored. Mitofusin 2 (Mfn2) is a highly conserved transmembrane GTPase. Our previous study demonstrated that the upregulation of Mfn2 can inhibit pulmonary fibrosis in ARDS mice. In this investigation, we identified upstream miRNAs regulating Mfn2 using bioinformatics tools such as TargetScan, miRDB, and microT-CDS. Based on the expression levels of these miRNAs in lung tissue from rats with LPS-induced ARDS, miR-93-5p was selected as the focus of our research. We modulated miR-93-5p expression in ARDS rats via tail vein injection of a miR-93-5p antagomir. Thereafter, we conducted pathological staining and molecular assays to examine the impact of miR-93-5p on pulmonary fibrosis in ARDS rats and to elucidate its potential mechanisms. The results demonstrated that the expression of miR-93-5p was significantly upregulated in the lung tissue of ARDS rats. LPS-induced ARDS rats exhibited severe pulmonary fibrosis, inflammation, and strong endoplasmic reticulum (ER) stress. Furthermore, Mfn2 expression exhibited a negative correlation with miR-93-5p expression. Inhibition of miR-93-5p markedly upregulated Mfn2 expression, attenuated ER stress and lung inflammation, and decreased collagen deposition. In conclusion, the inhibition of miR-93-5p upregulated Mfn2 expression and attenuated ER stress, consequently ameliorating pulmonary fibrosis in ARDS rats. Key words Acute respiratory distress syndrome " miR-93-5p " Pulmonary fibrosis " Endoplasmic reticulum stress " Mitofusin 2.