A Translational Model for Venous Thromboembolism: MicroRNA Expression in Hibernating Black Bears
Dickson, Eric W.
Freedman, Jane E.
Cahan, Mitchell A.
UMass Chan AffiliationsDepartment of Pediatrics
Mueller Lab for Gene Therapy, Horae Gene Therapy Center
Department of Emergency Medicine
Division of Cardiovascular Medicine, Department of Medicine
Program in Molecular Medicine
Department of Surgery
Document TypeJournal Article
Biological Phenomena, Cell Phenomena, and Immunity
Circulatory and Respiratory Physiology
Genetics and Genomics
Nucleic Acids, Nucleotides, and Nucleosides
Translational Medical Research
MetadataShow full item record
AbstractBACKGROUND: Hibernating American black bears have significantly different clotting parameters than their summer active counterparts, affording them protection against venous thromboembolism during prolonged periods of immobility. We sought to evaluate if significant differences exist between the expression of microRNAs in the plasma of hibernating black bears compared with their summer active counterparts, potentially contributing to differences in hemostasis during hibernation. MATERIALS AND METHODS: MicroRNA sequencing was assessed in plasma from 21 American black bears in summer active (n = 11) and hibernating states (n = 10), and microRNA signatures during hibernating and active state were established using both bear and human genome. MicroRNA targets were predicted using messenger RNA (mRNA) transcripts from black bear kidney cells. In vitro studies were performed to confirm the relationship between identified microRNAs and mRNA expression, using artificial microRNA and human liver cells. RESULTS: Using the bear genome, we identified 15 microRNAs differentially expressed in the plasma of hibernating black bears. Of these microRNAs, three were significantly downregulated (miR-141-3p, miR-200a-3p, and miR-200c-3p), were predicted to target SERPINC1, the gene for antithrombin, and demonstrated regulatory control of the gene mRNA expression in cell studies. CONCLUSIONS: Our findings suggest that the hibernating black bears' ability to maintain hemostasis and achieve protection from venous thromboembolism during prolonged periods of immobility may be due to changes in microRNA signatures and possible upregulation of antithrombin expression.
Fazzalari A, Basadonna G, Kucukural A, Tanriverdi K, Koupenova M, Pozzi N, Kakuturu J, Friedrich AU, Korstanje R, Fowler N, Belant JL, Beyer DE Jr, Brooks MB, Dickson EW, Blackwood M, Mueller C, Palesty JA, Freedman JE, Cahan MA. A Translational Model for Venous Thromboembolism: MicroRNA Expression in Hibernating Black Bears. J Surg Res. 2020 Aug 25;257:203-212. doi: 10.1016/j.jss.2020.06.027. Epub ahead of print. PMID: 32858321. Link to article on publisher's site
Permanent Link to this Itemhttp://hdl.handle.net/20.500.14038/29578
Full author list omitted for brevity. For the full list of authors, see article.