MiR-665 inhibits inflammatory response in microglia following spinal cord injury by targeting TREM2

S. Liu, X.-M. Li, J.-B. Yuan, L.-L. Li, C. Wang, X.-M. Lin, X. Miao, Z.-C. Shi

Department of Orthopaedics, Changhai Hospital, Second Military Medical University, Shanghai, China. zhicaishi@vip.sina.com

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• Orthopedics

OBJECTIVE: The purpose of this study was to uncover the role of microRNA-665 (miR-665) in protecting inflammatory response in microglia following spinal cord injury (SCI) and the underlying mechanism.

PATIENTS AND METHODS: The serum levels of miR-665 and TREM2 (triggering receptor expressed on myeloid 2) in SCI patients (n=24) and healthy subjects (n=24) were detected by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). Then, the serum levels of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) were detected by enzyme-linked immunosorbent assay (ELISA). After lipopolysaccharide (LPS) induction in BV2 cells, the relative levels of miR-665 and TREM2 were detected by qRT-PCR, and relative levels of IL-6 and TNF-α in the culture medium were examined by ELISA. Next, TREM2, the target gene of miR-665, was determined by Dual-Luciferase reporter assay, and the relationship between the expression levels of TREM2 and miR-665 in SCI patients and BV2 cells was analyzed. Finally, the regulatory effects of miR-665 and TREM2 on IL-6 and TNF-α levels in the culture medium of LPS-induced BV2 cells were assessed.

RESULTS: It was found that miR-665 was downregulated in serum of SCI patients and LPS-induced BV2 cells, while TREM2 was upregulated. Silenced miR-665 or overexpressed TREM2 was involved in protecting inflammatory response following SCI. Besides, rescue experiments showed that miR-665 participated in the regulation of inflammatory response following SCI by targeting TREM2.

CONCLUSIONS: MiR-665 inhibits inflammatory response following SCI by targeting TREM2.

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