PMID- 36658478 OWN - NLM STAT- MEDLINE DCOM- 20230124 LR - 20230124 IS - 1689-1392 (Electronic) IS - 1425-8153 (Print) IS - 1425-8153 (Linking) VI - 28 IP - 1 DP - 2023 Jan 19 TI - Photobiomodulation promotes spinal cord injury repair by inhibiting macrophage polarization through lncRNA TUG1-miR-1192/TLR3 axis. PG - 5 LID - 10.1186/s11658-023-00417-0 [doi] LID - 5 AB - BACKGROUND: Secondary spinal cord injury (SCI) often causes the aggravation of inflammatory reaction and nerve injury, which affects the recovery of motor function. Bone-marrow-derived macrophages (BMDMs) were recruited to the injured area after SCI, and the M1 polarization is the key process for inducing inflammatory response and neuronal apoptosis. We previously showed that photobiomodulation (PBM) can inhibit the polarization of M1 phenotype of BMDMs and reduce inflammation, but the underlying mechanisms are unclear. The purpose of this study is to explore the potential target and mechanism of PBM in treating SCI. METHODS: Transcriptome sequencing and bioinformatics analysis showed that long noncoding RNA taurine upregulated gene 1 (lncRNA TUG1) was a potential target of PBM. The expression and specific mechanism of lncRNA TUG1 were detected by qPCR, immunofluorescence, flow cytometry, western blotting, fluorescence in situ hybridization, and luciferase assay. The Basso mouse scale (BMS) and gait analysis were used to evaluate the recovery of motor function in mice. RESULTS: Results showed that lncRNA TUG1 may be a potential target of PBM, regulating the polarization of BMDMs, inflammatory response, and the axial growth of DRG. Mechanistically, TUG1 competed with TLR3 for binding to miR-1192 and attenuated the inhibitory effect of miR-1192 on TLR3. This effect protected TLR3 from degradation, enabling the high expression of TLR3, which promoted the activation of downstream NF-kappaB signal and the release of inflammatory cytokines. In vivo, PBM treatment could reduce the expression of TUG1, TLR3, and inflammatory cytokines and promoted nerve survival and motor function recovery in SCI mice. CONCLUSIONS: Our study clarified that the lncRNA TUG1/miR-1192/TLR3 axis is an important pathway for PBM to inhibit M1 macrophage polarization and inflammation, which provides theoretical support for its clinical application in patients with SCI. CI - (c) 2023. The Author(s). FAU - Ju, Cheng AU - Ju C AD - Department of Orthopedics, Xijing Hospital, Fourth Military Medical University, Changle West Road No. 127, Xi'an, 710032, Shaanxi, China. FAU - Ma, Yangguang AU - Ma Y AD - Department of Orthopedics, Xijing Hospital, Fourth Military Medical University, Changle West Road No. 127, Xi'an, 710032, Shaanxi, China. FAU - Zuo, Xiaoshuang AU - Zuo X AD - Department of Orthopedics, Xijing Hospital, Fourth Military Medical University, Changle West Road No. 127, Xi'an, 710032, Shaanxi, China. FAU - Wang, Xuankang AU - Wang X AD - Department of Orthopedics, Xijing Hospital, Fourth Military Medical University, Changle West Road No. 127, Xi'an, 710032, Shaanxi, China. FAU - Song, Zhiwen AU - Song Z AD - Department of Orthopedics, Xijing Hospital, Fourth Military Medical University, Changle West Road No. 127, Xi'an, 710032, Shaanxi, China. FAU - Zhang, Zhihao AU - Zhang Z AD - Department of Orthopedics, Xijing Hospital, Fourth Military Medical University, Changle West Road No. 127, Xi'an, 710032, Shaanxi, China. FAU - Zhu, Zhijie AU - Zhu Z AD - Department of Orthopedics, Xijing Hospital, Fourth Military Medical University, Changle West Road No. 127, Xi'an, 710032, Shaanxi, China. FAU - Li, Xin AU - Li X AD - Department of Orthopedics, Xijing Hospital, Fourth Military Medical University, Changle West Road No. 127, Xi'an, 710032, Shaanxi, China. FAU - Liang, Zhuowen AU - Liang Z AD - Department of Orthopedics, Xijing Hospital, Fourth Military Medical University, Changle West Road No. 127, Xi'an, 710032, Shaanxi, China. FAU - Ding, Tan AU - Ding T AD - Department of Orthopedics, Xijing Hospital, Fourth Military Medical University, Changle West Road No. 127, Xi'an, 710032, Shaanxi, China. FAU - Hu, Xueyu AU - Hu X AD - Department of Orthopedics, Xijing Hospital, Fourth Military Medical University, Changle West Road No. 127, Xi'an, 710032, Shaanxi, China. huxueyu@fmmu.edu.cn. FAU - Wang, Zhe AU - Wang Z AD - Department of Orthopedics, Xijing Hospital, Fourth Military Medical University, Changle West Road No. 127, Xi'an, 710032, Shaanxi, China. wangzhe@fmmu.edu.cn. LA - eng GR - NO.81070996/National Natural Scientific Foundation of China/ GR - NO.81572151/National Natural Scientific Foundation of China/ GR - NO.2020ZDLSF02-05/Shaanxi Provincial Key R&D Program/ GR - NO.2021ZDLSF02-10/Shaanxi Provincial Key R&D Program/ GR - 2018RCFC02/The Everest Project of Fourth Military Medical University/ GR - XJZT19Z22/Discipline Boost Project of the First Affiliated Hospital of Air Force Military Medical University/ GR - XJZT21L01/Discipline Boost Project of the First Affiliated Hospital of Air Force Military Medical University/ PT - Journal Article DEP - 20230119 PL - England TA - Cell Mol Biol Lett JT - Cellular & molecular biology letters JID - 9607427 RN - 0 (Cytokines) RN - 0 (MicroRNAs) RN - 0 (MIRN1192 microRNA, mouse) RN - 0 (RNA, Long Noncoding) RN - 0 (TLR3 protein, mouse) RN - 0 (Toll-Like Receptor 3) RN - 0 (TUG1 noncoding RNA, mouse) SB - IM MH - Animals MH - Mice MH - Cytokines/genetics MH - In Situ Hybridization, Fluorescence MH - Inflammation/genetics/metabolism MH - Macrophages/metabolism MH - *MicroRNAs/genetics/metabolism MH - *RNA, Long Noncoding/genetics/metabolism MH - *Spinal Cord Injuries/genetics MH - *Toll-Like Receptor 3/genetics PMC - PMC9854040 OTO - NOTNLM OT - Bone-marrow-derived macrophages OT - Inflammation OT - Long noncoding RNA TUG1 OT - Photobiomodulation OT - Spinal cord injury OT - Transcriptome sequencing COIS- The authors declare no competing interests. EDAT- 2023/01/20 06:00 MHDA- 2023/01/24 06:00 PMCR- 2023/01/19 CRDT- 2023/01/19 23:43 PHST- 2022/11/09 00:00 [received] PHST- 2023/01/05 00:00 [accepted] PHST- 2023/01/19 23:43 [entrez] PHST- 2023/01/20 06:00 [pubmed] PHST- 2023/01/24 06:00 [medline] PHST- 2023/01/19 00:00 [pmc-release] AID - 10.1186/s11658-023-00417-0 [pii] AID - 417 [pii] AID - 10.1186/s11658-023-00417-0 [doi] PST - epublish SO - Cell Mol Biol Lett. 2023 Jan 19;28(1):5. doi: 10.1186/s11658-023-00417-0.