title: microRNAs mediate oleic acid-induced acute lung injury in rats using an alternative injury mechanism.
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.
authors.affiliation: Department 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.
authors.forename: Sang Mook
authors.initials: SM
authors.lastname: Lee
authors.affiliation: Clinical Research Institute, Daejeon St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seocho-gu, Seoul 137‑701, Republic of Korea.
authors.forename: Hyunsoo
authors.initials: H
authors.lastname: Choi
authors.affiliation: Clinical Research Institute, Daejeon St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seocho-gu, Seoul 137‑701, Republic of Korea.
authors.forename: Geumjin
authors.initials: G
authors.lastname: Yang
authors.affiliation: Clinical Research Institute, Daejeon St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seocho-gu, Seoul 137‑701, Republic of Korea.
authors.forename: Ki Cheol
authors.initials: KC
authors.lastname: Park
authors.affiliation: Department of Emergency Medicine, Daejeon St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seocho-gu, Seoul 137‑701, Republic of Korea.
authors.forename: Sikyoung
authors.initials: S
authors.lastname: Jeong
authors.affiliation: Department of Emergency Medicine, Daejeon St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seocho-gu, Seoul 137‑701, Republic of Korea.
authors.forename: Sungyoup
authors.initials: S
authors.lastname: Hong
mesh_terms: D020413:3' Untranslated Regions; D000199:Actins / Q000378:metabolism; D055371:Acute Lung Injury / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D000818:Animals; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000187:drug effects; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D018793:Interleukin-13 / Q000378:metabolism; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D008168:Lung / Q000378:metabolism; D008297:Male; D035683:MicroRNAs / Q000378:metabolism*; D019301:Oleic Acid / Q000633:toxicity*; D051059:PTEN Phosphohydrolase / Q000235:genetics / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D020413:3' Untranslated Regions; D000199:Actins; D048049:Extracellular Signal-Regulated MAP Kinases; D018793:Interleukin-13; D048031:JNK Mitogen-Activated Protein Kinases; D035683:MicroRNAs; D019301:Oleic Acid; D051059:PTEN Phosphohydrolase; D051057:Proto-Oncogene Proteins c-akt; C498862:Acta2 protein, rat