PMID- 30513512 OWN - NLM STAT- MEDLINE DCOM- 20190121 LR - 20190212 IS - 1421-9778 (Electronic) IS - 1015-8987 (Linking) VI - 51 IP - 4 DP - 2018 TI - miRNA-544a Regulates the Inflammation of Spinal Cord Injury by Inhibiting the Expression of NEUROD4. PG - 1921-1931 LID - 10.1159/000495717 [doi] AB - BACKGROUND/AIMS: To explore the potential role of miR-544a in spinal cord injury and the possible mechanism involved. METHODS: We established a mouse model with spinal cord injury to examine the changes in grip force recovery of the forelimb or the posterior limb of the mouse. Microarray was performed to achieve differentiated miRNAs in the mice. The expressions of miR-544a, MCP-1, IL36B and IL17B after spinal cord injury were detected by qRT-PCR. Subsequently, miR-544a was overexpressed to observe changes in inflammation and grip strength after spinal cord injury. Target gene of miR-544a was then predicted using bioinformatics technology. Finally, dual luciferase reporter gene assay was used to verify the binding of miR-544a to its target gene. RESULTS: Using mice models with spinal cord injury, we found that the strength of their four limbs began to recover 7 days after injury. The results of microarray and qRT-PCR confirmed that mir-544a level in mice with spinal cord injury decreased with increase of injury time, while the levels of inflammatory genes MCP-1 (monocyte chemoattractant protein-1), IL1 (interleukin-1) and TNF-alpha (tumor necrosis factor alpha) IL36B (interleukin-36 beta) and IL17B (interleukin-17 beta) were significantly increased. However, overexpression of miR-544a in the mice significantly reduced the level of inflammation and restored their grip strength in their four limbs. Finally, we found that miR-544a can bind to the NEUROD4 (Neurogenic differentiation 4) 3'UTR (Untranslated Region) region through bioinformatics website prediction, which was further confirmed by dual luciferase reporter assay. NEUROD4 level was significantly reduced following the overexpression of miR-544a. CONCLUSION: The expression of miR-544a was significantly decreased after spinal cord injury. High expression of miR-544a could alleviate the inflammation caused by spinal cord injury and promote the recovery of spinal cord via the inhibition of NEUROD4. CI - (c) 2018 The Author(s). Published by S. Karger AG, Basel. FAU - Yang, Lei AU - Yang L AD - Department of Orthopaedics, Nanjing First Hospital, Nanjing Medical University, Nanjing, China. FAU - Ge, Dawei AU - Ge D AD - Department of Orthopaedics, the First Affiliated Hospital of Nanjing Medical University, Nanjing, China. FAU - Chen, Xi AU - Chen X AD - Department of Orthopaedics, Nanjing First Hospital, Nanjing Medical University, Nanjing, China. FAU - Jiang, Chunzhi AU - Jiang C AD - Department of Orthopaedics, Nanjing First Hospital, Nanjing Medical University, Nanjing, China. FAU - Zheng, Shengnai AU - Zheng S AD - Department of Orthopaedics, Nanjing First Hospital, Nanjing Medical University, Nanjing, Chinaleiyangspine@163.com. LA - eng PT - Journal Article DEP - 20181204 PL - Germany TA - Cell Physiol Biochem JT - Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology JID - 9113221 RN - 0 (3' Untranslated Regions) RN - 0 (Basic Helix-Loop-Helix Transcription Factors) RN - 0 (MIRN-544 microRNA, mouse) RN - 0 (MicroRNAs) RN - 0 (Nerve Tissue Proteins) RN - 0 (Neurod4 protein, mouse) SB - IM MH - 3' Untranslated Regions MH - Animals MH - Basic Helix-Loop-Helix Transcription Factors/*genetics/immunology MH - *Down-Regulation MH - Female MH - Inflammation/*genetics/immunology/pathology MH - Mice MH - Mice, Inbred C57BL MH - MicroRNAs/*genetics/immunology MH - Nerve Tissue Proteins/*genetics/immunology MH - Spinal Cord/immunology/pathology MH - Spinal Cord Injuries/*genetics/immunology/pathology MH - Up-Regulation OTO - NOTNLM OT - Inflammation OT - NEUROD4 OT - Spinal cord injury OT - miR-544a EDAT- 2018/12/05 06:00 MHDA- 2019/01/22 06:00 CRDT- 2018/12/05 06:00 PHST- 2018/03/09 00:00 [received] PHST- 2018/11/23 00:00 [accepted] PHST- 2018/12/05 06:00 [pubmed] PHST- 2019/01/22 06:00 [medline] PHST- 2018/12/05 06:00 [entrez] AID - 000495717 [pii] AID - 10.1159/000495717 [doi] PST - ppublish SO - Cell Physiol Biochem. 2018;51(4):1921-1931. doi: 10.1159/000495717. Epub 2018 Dec 4.