PMID- 37534324 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20230804 IS - 2405-5808 (Electronic) IS - 2405-5808 (Linking) VI - 35 DP - 2023 Sep TI - Umbilical mesenchymal stem cell-derived exosomes promote spinal cord functional recovery through the miR-146b/TLR4 -mediated NF-kappaB p65 signaling pathway in rats. PG - 101497 LID - 10.1016/j.bbrep.2023.101497 [doi] LID - 101497 AB - Spinal cord injury (SCI) is an incurable central nervous system impairment that lack of efficient treatment. Exosomes derived from mesenchymal stem cells (MSCs) are widely applied in disease treatment. This work aimed to determine the promising therapeutic effects of MSC-derived exosomal miRNA146b on SCI. A rat spinal cord injury (SCI) model and lipopolysaccharide (LPS)-induced PC12 cell model were established. Exosomes were extracted from human umbilical cord mesenchymal stem cells (hUCMSCs). The identification of exosomes was performed by using transmission electronic microscope (TEM) and nanoparticle tracking analysis (NTA). Hematoxylin and eosin (HE) staining and TUNEL assay were performed to assess tissue damage and apoptosis, respectively. ELISA was performed to detect levels of inflammatory cytokines. Cell viability was checked by cell counting kit 8 (CCK-8). Gene expression and protein levels were detected by qPCR and western blotting assay. The interaction between miR-146 b and Toll-like receptor 4 (TLR4) was assessed by luciferase reporter gene assay. The hUCMSC-derived exosomes could notably alleviate the spinal cord injury and cell apoptosis. The exosomal miR-146 b treatment suppressed the release of IL-1 beta, IL-6, and TNFalpha. The miR-146 b suppressed the expression of TLR4, directly interact with the 3'-untranslated region (3'UTR) of TLR4, and inactivated the nuclear factor kappaB (NF-kappaB) signaling. The hUCMSCs-derived exosomal miR-146 b protects neurons from spinal cord injury through targeting the TLR4 and inactivating the NF-kappaB signaling. Our findings supported the application of hUCMSCs-derived exosomal miR-146 b for the protection of SCI. CI - (c) 2023 Everunion Biotechnology Co., LTD. Tianjin. FAU - Wang, Xiujuan AU - Wang X AD - Technology Department, Everunion Biotechnology Co. LTD, Tianjin, China. FAU - Yang, Ying AU - Yang Y AD - Technology Department, Everunion Biotechnology Co. LTD, Tianjin, China. FAU - Li, Wei AU - Li W AD - Technology Department, Everunion Biotechnology Co. LTD, Tianjin, China. FAU - Hao, MingYuan AU - Hao M AD - Technology Department, Everunion Biotechnology Co. LTD, Tianjin, China. FAU - Xu, YongSheng AU - Xu Y AD - Technology Department, Everunion Biotechnology Co. LTD, Tianjin, China. LA - eng PT - Journal Article DEP - 20230720 PL - Netherlands TA - Biochem Biophys Rep JT - Biochemistry and biophysics reports JID - 101660999 PMC - PMC10393557 OTO - NOTNLM OT - Exosomes OT - Mesenchymal stem cell OT - Spinal cord injury OT - Toll-like receptor 4 OT - miR-146b COIS- There are no conflicts of interest. EDAT- 2023/08/03 06:42 MHDA- 2023/08/03 06:43 PMCR- 2023/07/20 CRDT- 2023/08/03 04:29 PHST- 2023/01/09 00:00 [received] PHST- 2023/06/01 00:00 [revised] PHST- 2023/06/05 00:00 [accepted] PHST- 2023/08/03 06:43 [medline] PHST- 2023/08/03 06:42 [pubmed] PHST- 2023/08/03 04:29 [entrez] PHST- 2023/07/20 00:00 [pmc-release] AID - S2405-5808(23)00078-X [pii] AID - 101497 [pii] AID - 10.1016/j.bbrep.2023.101497 [doi] PST - epublish SO - Biochem Biophys Rep. 2023 Jul 20;35:101497. doi: 10.1016/j.bbrep.2023.101497. eCollection 2023 Sep.