Exosomal miR-17-92 Cluster from BMSCs Alleviates Apoptosis and Inflammation in Spinal Cord Injury

被引:0
作者
Wang, Wei [1 ]
Yao, Fei [2 ]
Xing, Haiyuan [1 ]
Yang, Fan [1 ]
Yan, Li [1 ]
机构
[1] Wuhan Fourth Hosp, Dept Orthoped, 473 Hanzheng St, Wuhan 430033, Peoples R China
[2] Wuhan Sports Univ, Wuhan 430079, Peoples R China
关键词
miR-17-92; cluster; Exosomes; Spinal cord injury; Apoptosis; NEUROGENESIS;
D O I
10.1007/s10528-024-10876-5
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Spinal cord injury (SCI) involves neuronal apoptosis and axonal disruption, leading to severe motor dysfunction. Studies indicate that exosomes transport microRNAs (miRNAs) and play a crucial role in intercellular communication. This study aimed to explore whether the bone marrow mesenchymal stem cell (BMSCs)-exosomal miR-17-92 cluster can protect against SCI and to explain the underlying mechanisms. In vivo and in vitro SCI models were established and treated with control exosomes (con-exo) or exosomes derived from BMSCs transfected with miR-17-92 cluster plasmid (miR-17-92-exo). Rat BMSCs were isolated and positive markers were identified by flow cytometry. BMSC-derived exosomes were extracted and verified using transmission electron microscopy (TEM), nanoparticle tracking analysis (NTA), and western blotting. The expression of the miR-17-92 cluster was validated by quantitative reverse transcription PCR (qRT-PCR). Spinal cord function, histopathological changes, apoptotic cells, and inflammatory cytokines release in spinal cord tissues were assessed using the Basso-Beattie-Bresnahan (BBB) score, hematoxylin and eosin (HE) staining, terminal deoxynucleotide transferase (TdT)-mediated dUTP nick-end labeling (TUNEL) staining, enzyme-linked immunosorbent assay (ELISA), and qRT-PCR. In PC12 cells, cell proliferation, apoptosis, apoptosis-related proteins cleaved-Caspase3 expression, and inflammatory factors secretion were analyzed using a cell counting kit-8 (CCK8) assay, flow cytometry, western blotting, and ELISA. Our data revealed that the exosomes were successfully isolated from rat BMSCs. The BMSC-exosomal miR-17-92 cluster improved neural functional recovery after SCI, as evidenced by an increased BBB score, improved pathological damage, reduced neuronal apoptosis, and decreased inflammatory factors release. Additionally, miR-17-92-exo treatment significantly inhibited lipopolysaccharide (LPS)-induced reduction in cell viability, increase in cell apoptosis, and upregulation of inflammatory factors in PC12 cells. The exosomal miR-17-92 cluster derived from BMSCs improved functional recovery and exhibited neuroprotective effects in SCI by alleviating apoptosis and inflammation.
引用
收藏
页数:15
相关论文
共 30 条
[21]   Exosomes-mediated transfer of LINC00691 regulates the formation of CAFs and promotes the progression of gastric cancer [J].
Xia, Bin ;
Gu, Xiuyu ;
Xu, Tingting ;
Yan, Meina ;
Huang, Lan ;
Jiang, Chun ;
Li, Meifen ;
Zhai, Guanghua ;
Zhang, Guoping ;
Wu, Jian ;
Zhou, Yu ;
Sun, Chunrong ;
Liang, Wei .
BMC CANCER, 2023, 23 (01)
[22]   MicroRNA cluster miR-17-92 Cluster in Exosomes Enhance Neuroplasticity and Functional Recovery After Stroke in Rats [J].
Xin, Hongqi ;
Katakowski, Mark ;
Wang, Fengjie ;
Qian, Jian-Yong ;
Liu, Xian Shuang ;
Ali, Meser M. ;
Buller, Benjamin ;
Zhang, Zheng Gang ;
Chopp, Michael .
STROKE, 2017, 48 (03) :747-753
[23]   Treg cell-derived exosomes miR-709 attenuates microglia pyroptosis and promotes motor function recovery after spinal cord injury [J].
Xiong, Wu ;
Li, Cong ;
Kong, Guang ;
Zeng, Qiang ;
Wang, Siming ;
Yin, Guoyong ;
Gu, Jun ;
Fan, Jin .
JOURNAL OF NANOBIOTECHNOLOGY, 2022, 20 (01)
[24]   The role of the miR-17-92 cluster in neurogenesis and angiogenesis in the central nervous system of adults [J].
Yang, Ping ;
Cai, Linghu ;
Zhang, Guan ;
Bian, Zhiqun ;
Han, Gaofeng .
JOURNAL OF NEUROSCIENCE RESEARCH, 2017, 95 (08) :1574-1581
[25]   Imatinib inhibits pericyte-fibroblast transition and inflammation and promotes axon regeneration by blocking the PDGF-BB/PDGFRβ pathway in spinal cord injury [J].
Yao, Fei ;
Luo, Yang ;
Liu, Yan-Chang ;
Chen, Yi-Hao ;
Li, Yi-Teng ;
Hu, Xu-Yang ;
You, Xing-Yu ;
Yu, Shui-Sheng ;
Li, Zi-Yu ;
Chen, Lei ;
Tian, Da-Sheng ;
Zheng, Mei-Ge ;
Cheng, Li ;
Jing, Jue-Hua .
INFLAMMATION AND REGENERATION, 2022, 42 (01)
[26]   MicroRNAs in spinal cord injury: A narrative review [J].
Zhang, Chunjia ;
Talifu, Zuliyaer ;
Xu, Xin ;
Liu, Wubo ;
Ke, Han ;
Pan, Yunzhu ;
Li, Yan ;
Bai, Fan ;
Jing, Yingli ;
Li, Zihan ;
Li, Zehui ;
Yang, Degang ;
Gao, Feng ;
Du, Liangjie ;
Li, Jianjun ;
Yu, Yan .
FRONTIERS IN MOLECULAR NEUROSCIENCE, 2023, 16
[27]   MicroRNA-223 targets NLRP3 to relieve inflammation and alleviate spinal cord injury [J].
Zhang, Meng ;
Wang, Lin ;
Huang, Sihua ;
He, Xijing .
LIFE SCIENCES, 2020, 254
[28]   Biology of MiR-17-92 Cluster and Its Progress in Lung Cancer [J].
Zhang, Xinju ;
Li, Yanli ;
Qi, Pengfei ;
Ma, Zhongliang .
INTERNATIONAL JOURNAL OF MEDICAL SCIENCES, 2018, 15 (13) :1443-1448
[29]   miR-495 reduces neuronal cell apoptosis and relieves acute spinal cord injury through inhibiting PRDM5 [J].
Zhang, Yan ;
Wang, Shanshan ;
Li, Hongli ;
Xu, Xia .
JOURNAL OF MOLECULAR HISTOLOGY, 2021, 52 (02) :385-396
[30]   MiR-17-92 Cluster-Enriched Exosomes Derived from Human Bone Marrow Mesenchymal Stromal Cells Improve Tissue and Functional Recovery in Rats after Traumatic Brain Injury [J].
Zhang, Yanlu ;
Zhang, Yi ;
Chopp, Michael ;
Pang, Haiyan ;
Zhang, Zheng Gang ;
Mahmood, Asim ;
Xiong, Ye .
JOURNAL OF NEUROTRAUMA, 2021, 38 (11) :1535-1550