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Updated: May 1, 2026
Mouse Model of Oleic Acid-Induced Acute Respiratory Distress Syndrome
Published on: June 2, 2022
microRNAs mediate oleic acid-induced acute lung injury in rats using an alternative injury mechanism
Sang Mook Lee1, Hyunsoo Choi2, Geumjin Yang2
1Department of Anaesthesia and Pain Medicine, Daejeon St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seocho-gu, Seoul 137‑701, Republic of Korea.
Abstract:
Intravenous (IV) infusion of oleic acid (OA) distributes OA microemboli in the pulmonary capillaries, which results in severe vascular congestion, hemorrhage vascular congestion, interstitial edema, intravascular coagulation and bleeding. The immune response to acute lung injury (ALI) is known to be associated with rapid and widespread changes in microRNA (miRNA) expression in the lung. The present study of a model of rat lung injury aimed to investigate how the lung miRNA profile changes to mediate ALI. For the induction of ALI, OA (200 µl/kg) suspended in 20% ethyl alcohol was injected through the tail vein for 20 min. Lung tissue samples were acquired at 3, 6 and 24 h, and miRNA microarray and quantitative polymerase chain reaction were performed using these samples. The activation of phosphatase and tensin homolog (PTEN), protein kinase B (Akt), extracellular signal-regulated kinases (ERK) and c-Jun N-terminal kinases (JNK) were analyzed by western blot analysis. There were 75 miRNAs that demonstrated >1.5‑fold changes in expression levels. miR-101a was highly upregulated at 3 h. miR-21 was upregulated in the OA group throughout the 24 h following OA challenge. miR-1 was the most downregulated miRNA at 24 h. In order to examine the expression levels of PTEN and Akt as targets of miR-21, western blot analysis was performed. At 3 h, the levels of PTEN were attenuated in the OA group as compared with those in the control group; however, p-Akt/Akt levels were increased at 3 h for the OA group. PTEN and p-Akt/Akt were significantly higher in the OA group at 3 h and were rapidly decreased at 6 h. The immunohistochemical stain of α-smooth muscle actin in the bronchial and alveolar wall increased 24 h after OA‑induced ALI. These results indicated that the profile of miRNAs dynamically changed throughout the OA-induced ALI process, and mitogen-activated protein kinase activation, PTEN/Akt pathway alteration and smooth muscle actin activation were observed in this ALI model.
Insights
Oleic acid (OA) infusion causes acute lung injury (ALI) by altering microRNA (miRNA) profiles. Researchers identified specific miRNA changes and pathway activations involved in the OA-induced ALI immune response.
Area of Science:
- Pulmonary Medicine
- Molecular Biology
- Immunology
Background:
- Acute lung injury (ALI) induced by oleic acid (OA) involves complex immune responses and significant changes in lung microRNA (miRNA) expression.
- Understanding these miRNA dynamics is crucial for elucidating the mechanisms underlying OA-induced ALI.
Purpose of the Study:
- To investigate the dynamic changes in the lung miRNA profile during the development of OA-induced ALI in a rat model.
- To identify specific miRNAs and signaling pathways involved in mediating the inflammatory response to OA.
Main Methods:
- Acute lung injury was induced in rats via intravenous infusion of oleic acid (OA).
- Lung tissue was collected at 3, 6, and 24 hours post-infusion for miRNA microarray and quantitative polymerase chain reaction.
- Western blot analysis was used to assess the activation of key signaling proteins, including PTEN, Akt, ERK, and JNK, and immunohistochemistry for α-smooth muscle actin.
Main Results:
- A total of 75 miRNAs showed significant expression changes (>1.5-fold).
- miR-21 was consistently upregulated throughout the 24-hour period, while miR-101a was upregulated early (3h) and miR-1 was downregulated late (24h).
- OA-induced ALI involved alterations in the PTEN/Akt pathway, activation of MAPK signaling (ERK, JNK), and increased α-smooth muscle actin expression.
Conclusions:
- The miRNA profile in the lung undergoes dynamic changes during OA-induced ALI.
- Specific miRNAs, such as miR-21, play a significant role in the inflammatory cascade.
- The study highlights the involvement of the PTEN/Akt pathway and MAPK signaling in the pathogenesis of OA-induced ALI.
