A novel miRNA mimic attenuates organ injury after hepatic ischemia/reperfusion

• Published in: The journal of trauma and acute care surgery Vol. 94; no. 5; p. 702
• Main Authors: Borjas, Timothy, Jacob, Asha, Kobritz, Molly, Patel, Vihas, Coppa, Gene F, Aziz, Monowar, Wang, Ping
• Format: Journal Article
• Language: English
• Published: United States 01.05.2023
• Subjects: Animals; Apoptosis; Disease Models, Animal; Inflammation - metabolism; Ischemia - pathology; Liver - pathology; Liver Diseases - metabolism; Male; Mice; MicroRNAs - metabolism; Reperfusion; Reperfusion Injury - metabolism
• ISSN: 2163-0763
• DOI: 10.1097/TA.0000000000003877

Extracellular cold-inducible RNA-binding protein (eCIRP) is a novel mediator of inflammation and tissue injury. It has been shown that miRNA 130b-3p acts as an endogenous inhibitor of eCIRP. Because RNA mimics are unstable after in vivo administration, we have chemically engineered miRNA 130b-3p mimic (named PS-OMe miR130) to improve its stability by protection from nuclease activity. We hypothesize that PS-OMe miR130 reduces eCIRP-mediated injury and inflammation in a murine model of hepatic ischemia/reperfusion (I/R), a model of sterile inflammation. Adult male mice underwent 70% hepatic ischemia for 60 minutes and 24-hour reperfusion. At the start of reperfusion, mice were treated intravenously with vehicle (phosphate-buffered saline) or PS-OMe miR130. Blood and liver tissue were collected after 24 hours for biochemical analysis. Apoptosis in the liver tissue was determined by transferase dUTP nick-end labeling assay. After hepatic I/R, organ injury markers including aspartate aminotransferase, alanine aminotransferase, and lactate dehydrogenase significantly decreased after PS-OMe miR130 treatment. Furthermore, histological analysis of liver sections demonstrated significantly less injury in PS-OMe miR130 treatment mice versus vehicle mice. In addition, tumor necrosis factor α mRNA, interleukin-1β mRNA, and neutrophil infiltration (myeloperoxidase activity and granulocyte receptor 1 immunohistochemistry) were significantly attenuated after PS-OMe miR130 treatment. Finally, apoptosis significantly decreased in liver tissue after treatment. PS-OMe miR130 decreases eCIRP-mediated injury and inflammation in a murine model of hepatic I/R.