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The role of bone marrow microRNA (miR) in erythropoietic dysfunction after severe trauma
Authors:Camille G Apple  Elizabeth S Miller  Kolenkode B Kannan  Julie A Stortz  Tyler J Loftus  Maria Cecilia Lopez  Hari K Parvataneni  Matthew Patrick  Jennifer E Hagen  Henry V Baker  Philip A Efron  Alicia M Mohr
Institution:1. Department of Surgery and Sepsis and Critical Illness Research Center, University of Florida Health, Gainesville, FL;2. Department of Molecular Genetics and Microbiology, University of Florida, Gainesville, FL;3. Department of Orthopedic Surgery, University of Florida, Gainesville, FL
Abstract:BackgroundPrevious data has shown that severe traumatic injury is associated with bone marrow dysfunction, which manifests as persistent injury-associated anemia. This study sought to identify whether the expression of erythropoiesis-related microRNAs were altered in the bone marrow of trauma patients to determine if these microRNAs play a role in persistent injury-associated anemia.MethodsBone marrow was collected from severely injured trauma patients who underwent fracture fixation as well as patients who underwent elective hip replacement. There were 27 trauma patients and 10 controls analyzed. Total RNA and microRNA were isolated from CD34-positive cells using the RNeasy Plus Mini kit, and genome-wide microRNA expression patterns were assayed. Genes with significant expression differences were found using BRB-ArrayTools with a significance of P < .01.ResultsThere were marked differences in expression of 108 microRNAs in the trauma group when compared with hip replacement patients. Four of these microRNAs play a role in regulating erythropoiesis: microRNA-150, microRNA-223, microRNA15a, and microRNA-24. These microRNAs were all upregulated significantly, with trauma/hip replacement fold changes of 1.7, 1.8, 1.2, and 1.2 respectively, and all act to suppress or regulate erythropoiesis.ConclusionAssessment of the bone marrow microRNA profile in trauma patients compared to those undergoing elective hip replacement revealed the differential expression of microRNA-150, microRNA-223, microRNA-15a, and microRNA-24. These microRNAs all play a role in decreased erythroid progenitor cell growth and provide important insight to the erythropoietic dysfunction seen after trauma.
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