The role of bone marrow microRNA (miR) in erythropoietic dysfunction after severe trauma
Camille G Apple1, Elizabeth S Miller1, Kolenkode B Kannan1
1Department of Surgery and Sepsis and Critical Illness Research Center, University of Florida Health, Gainesville, FL.
Background:
Previous 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.
Methods:
Bone 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.
Results:
There 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.
Conclusion:
Assessment 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.
Insights
Severe trauma alters bone marrow microRNA expression, leading to persistent anemia. Specific microRNAs (miRNA-150, miRNA-223, miRNA-15a, miRNA-24) are upregulated, suppressing red blood cell production.
Area of Science:
- Hematology
- Molecular Biology
- Trauma Research
Background:
- Severe traumatic injury is linked to bone marrow dysfunction and persistent anemia.
- Erythropoiesis, the process of red blood cell production, can be impaired following trauma.
Purpose of the Study:
- To investigate alterations in erythropoiesis-related microRNA expression in trauma patients' bone marrow.
- To determine the role of these microRNAs in persistent injury-associated anemia.
Main Methods:
- Bone marrow samples were collected from trauma patients (n=27) and elective hip replacement controls (n=10).
- MicroRNA isolation from CD34-positive cells followed by genome-wide expression profiling.
- Differential gene expression analysis using BRB-ArrayTools (P < .01).
Main Results:
- Significant differences in 108 microRNAs were observed between trauma and control groups.
- Four key microRNAs involved in erythropoiesis regulation (miRNA-150, miRNA-223, miRNA-15a, miRNA-24) were upregulated in trauma patients.
- Fold changes for upregulated microRNAs ranged from 1.2 to 1.8.
Conclusions:
- Differential expression of miRNA-150, miRNA-223, miRNA-15a, and miRNA-24 was identified in trauma patients' bone marrow.
- These microRNAs contribute to decreased erythroid progenitor cell growth.
- Findings offer insight into the mechanisms of erythropoietic dysfunction post-trauma.
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