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Current Stem Cell Research & Therapy

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ISSN (Print): 1574-888X
ISSN (Online): 2212-3946

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Research Article

Differential Expression of microRNAs and Target Genes Analysis in Olfactory Ensheathing Cell-derived Extracellular Vesicles Versus Olfactory Ensheathing Cells

Author(s): Yubing Yang, Jiaxi Li, Weidong Liu, Dong Guo, Zhengchao Gao, Yingjie Zhao, Minchao Zhao, Xijing He* and Su’e Chang*

Volume 19, Issue 1, 2024

Published on: 03 May, 2023

Page: [116 - 125] Pages: 10

DOI: 10.2174/1574888X18666230418084900

Price: $65

Abstract

Introduction: Olfactory ensheathing cells (OECs) are important transplantable cells for the treatment of spinal cord injury. However, information on the mechanism of OEC-derived extracellular vesicles (EVs) in nerve repair is scarce.

Methods: We cultured OECs and extracted the OEC-derived EVs, which were identified using a transmission electron microscope, nanoparticle flow cytometry, and western blotting. High throughput RNA sequencing of OECs and OEC-EVs was performed, and the differentially expressed microRNAs (miRNAs) (DERs) were analyzed by bioinformatics. The target genes of DERs were identified using miRWalk, miRDB, miRTarBase, and TargetScan databases. Gene ontology and KEGG mapper tools were used to analyze the predicted target genes. Subsequently, the STRING database and Cytoscape software platform were used to analyze and construct miRNA target genes' protein-protein interaction (PPI) network.

Results: Overall, 206 miRNAs (105 upregulated and 101 downregulated) were differentially expressed in OEC-EVs (p < 0.05;|log2 (fold change)|>2). Six DERs (rno-miR-7a-5p, rno-miR-143-3p, rno-miR-182, rno-miR-214-3p, rno-miR-434-5p, rno-miR-543-3p) were significantly up-regulated , and a total of 974 miRNAs target genes were obtained. The target genes were mainly involved in biological processes such as regulation of cell size, positive regulation of cellular catabolic process and small GTPase-mediated signal transduction; positive regulation of genes involved in cellular components such as growth cone, site of polarized growth, and distal axon; and molecular functions such as small GTPase binding and Ras GTPase binding. In pathway analysis, target genes regulated by six DERs were mainly enriched in axon guidance, endocytosis, and Ras and cGMP-dependent protein kinase G signaling pathways. Finally, 19 hub genes were identified via the PPI network.

Conclusion: Our study provides a theoretical basis for treating nerve repair by OEC-derived EVs.

Keywords: Olfactory ensheathing cells, extracellular vesicles, microRNA, nerve repair, spinal cord injury, DERs.

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[1]
Rowland JW, Hawryluk GWJ, Kwon B, Fehlings MG. Current status of acute spinal cord injury pathophysiology and emerging therapies: promise on the horizon. Neurosurg Focus 2008; 25(5): E2.
[http://dx.doi.org/10.3171/FOC.2008.25.11.E2] [PMID: 18980476]
[2]
Tysseling-Mattiace VM, Sahni V, Niece KL, et al. Self-assembling nanofibers inhibit glial scar formation and promote axon elongation after spinal cord injury. J Neurosci 2008; 28(14): 3814-23.
[http://dx.doi.org/10.1523/JNEUROSCI.0143-08.2008] [PMID: 18385339]
[3]
Ramón-Cueto A, Cordero MI, Santos-Benito FF, Avila J. Functional recovery of paraplegic rats and motor axon regeneration in their spinal cords by olfactory ensheathing glia. Neuron 2000; 25(2): 425-35.
[http://dx.doi.org/10.1016/S0896-6273(00)80905-8] [PMID: 10719896]
[4]
Gao Z, Zhao Y, He X, et al. Transplantation of sh-miR-199a-5p-modified olfactory ensheathing cells promotes the functional recovery in rats with contusive spinal cord injury. Cell Transplant 2020; 29.
[http://dx.doi.org/10.1177/0963689720916173] [PMID: 32252553]
[5]
Gómez RM, Sánchez MY, Portela-Lomba M, et al. Cell therapy for spinal cord injury with olfactory ensheathing glia cells (OECs). Glia 2018; 66(7): 1267-301.
[http://dx.doi.org/10.1002/glia.23282] [PMID: 29330870]
[6]
Jiang Y, Guo J, Tang X, Wang X, Hao D, Yang H. The immunological roles of olfactory ensheathing cells in the treatment of spinal cord injury. Front Immunol 2022; 13: 881162.
[http://dx.doi.org/10.3389/fimmu.2022.881162] [PMID: 35669779]
[7]
Xu X, Liang Z, Lin Y, et al. Comparing the efficacy and safety of cell transplantation for spinal cord injury: A systematic review and bayesian network meta-analysis. Front Cell Neurosci 2022; 16: 860131.
[http://dx.doi.org/10.3389/fncel.2022.860131] [PMID: 35444516]
[8]
Wang X, Jiang C, Zhang Y, et al. The promoting effects of activated olfactory ensheathing cells on angiogenesis after spinal cord injury through the PI3K/Akt pathway. Cell Biosci 2022; 12(1): 23.
[http://dx.doi.org/10.1186/s13578-022-00765-y] [PMID: 35246244]
[9]
Conde-Vancells J, Rodriguez-Suarez E, Embade N, et al. Characterization and comprehensive proteome profiling of exosomes secreted by hepatocytes. J Proteome Res 2008; 7(12): 5157-66.
[http://dx.doi.org/10.1021/pr8004887] [PMID: 19367702]
[10]
Arraud N, Linares R, Tan S, et al. Extracellular vesicles from blood plasma: determination of their morphology, size, phenotype and con-centration. J Thromb Haemost 2014; 12(5): 614-27.
[http://dx.doi.org/10.1111/jth.12554] [PMID: 24618123]
[11]
Zhang J, Li S, Li L, et al. Exosome and exosomal microRNA: trafficking, sorting, and function. Genomics Proteomics Bioinformatics 2015; 13(1): 17-24.
[http://dx.doi.org/10.1016/j.gpb.2015.02.001] [PMID: 25724326]
[12]
Yang F, Ning Z, Ma L, et al. Exosomal miRNAs and miRNA dysregulation in cancer-associated fibroblasts. Mol Cancer 2017; 16(1): 148.
[http://dx.doi.org/10.1186/s12943-017-0718-4] [PMID: 28851377]
[13]
Heo JS, Kim S. Human adipose mesenchymal stem cells modulate inflammation and angiogenesis through exosomes. Sci Rep 2022; 12(1): 2776.
[http://dx.doi.org/10.1038/s41598-022-06824-1] [PMID: 35177768]
[14]
Bucan V, Vaslaitis D, Peck CT, Strauß S, Vogt PM, Radtke C. Effect of exosomes from rat adipose-derived mesenchymal stem cells on neurite outgrowth and sciatic nerve regeneration after crush injury. Mol Neurobiol 2019; 56(3): 1812-24.
[http://dx.doi.org/10.1007/s12035-018-1172-z] [PMID: 29931510]
[15]
Wei Z, Fan B, Ding H, et al. Proteomics analysis of Schwann cell-derived exosomes: a novel therapeutic strategy for central nervous sys-tem injury. Mol Cell Biochem 2019; 457(1-2): 51-9.
[http://dx.doi.org/10.1007/s11010-019-03511-0] [PMID: 30830528]
[16]
Yang P, Cai L, Zhang G, Bian Z, Han G. The role of the miR-17-92 cluster in neurogenesis and angiogenesis in the central nervous system of adults. J Neurosci Res 2017; 95(8): 1574-81.
[http://dx.doi.org/10.1002/jnr.23991] [PMID: 27869313]
[17]
Anders S, Huber W. Differential expression analysis for sequence count data. Genome Biol 2010; 11(10): R106.
[http://dx.doi.org/10.1186/gb-2010-11-10-r106] [PMID: 20979621]
[18]
Ashburner M, Ball CA, Blake JA, et al. Gene Ontology: tool for the unification of biology. Nat Genet 2000; 25(1): 25-9.
[http://dx.doi.org/10.1038/75556] [PMID: 10802651]
[19]
Kim T, Mehta SL, Morris-Blanco KC, et al. The microRNA miR-7a-5p ameliorates ischemic brain damage by repressing α-synuclein. Sci Signal 2018; 11(560): eaat4285.
[http://dx.doi.org/10.1126/scisignal.aat4285] [PMID: 30538177]
[20]
Zhou D, Huang Z, Zhu X, Hong T, Zhao Y. Circular RNA 0025984 ameliorates ischemic stroke injury and protects astrocytes through miR-143-3p/TET1/ORP150 pathway. Mol Neurobiol 2021; 58(11): 5937-53.
[http://dx.doi.org/10.1007/s12035-021-02486-8] [PMID: 34435328]
[21]
Soto A, Nieto-Díaz M, Reigada D, Barreda-Manso MA, Muñoz-Galdeano T, Maza RM. miR-182-5p regulates nogo-a expression and pro-motes neurite outgrowth of hippocampal neurons in vitro. Pharmaceuticals 2022; 15(5): 529.
[http://dx.doi.org/10.3390/ph15050529] [PMID: 35631355]
[22]
Liu L, Xu D, Wang T, et al. Epigenetic reduction of miR-214-3p upregulates astrocytic colony-stimulating factor-1 and contributes to neuropathic pain induced by nerve injury. Pain 2020; 161(1): 96-108.
[http://dx.doi.org/10.1097/j.pain.0000000000001681] [PMID: 31453981]
[23]
Li XZ, Lv CL, Shi JG, Zhang CX. MiR-543-3p promotes locomotor function recovery after spinal cord injury by inhibiting the expression of tumor necrosis factor superfamily member 15 in rats. Eur Rev Med Pharmacol Sci 2019; 23(7): 2701-9.
[PMID: 31002119]
[24]
Garcia-Martin R, Wang G, Brandão BB, et al. MicroRNA sequence codes for small extracellular vesicle release and cellular retention. Nature 2022; 601(7893): 446-51.
[http://dx.doi.org/10.1038/s41586-021-04234-3] [PMID: 34937935]
[25]
Demarco RS, Struckhoff EC, Lundquist EA. The Rac GTP exchange factor TIAM-1 acts with CDC-42 and the guidance receptor UNC-40/DCC in neuronal protrusion and axon guidance. PLoS Genet 2012; 8(4): e1002665.
[http://dx.doi.org/10.1371/journal.pgen.1002665] [PMID: 22570618]
[26]
Heidemann SR, Bray D. Tension-driven axon assembly: a possible mechanism. Front Cell Neurosci 2015; 9: 316.
[http://dx.doi.org/10.3389/fncel.2015.00316] [PMID: 26321917]
[27]
Kerstein PC, Nichol RH IV, Gomez TM. Mechanochemical regulation of growth cone motility. Front Cell Neurosci 2015; 9: 244.
[http://dx.doi.org/10.3389/fncel.2015.00244] [PMID: 26217175]
[28]
Antoine-Bertrand J, Villemure JF, Lamarche-Vane N. Implication of rho GTPases in neurodegenerative diseases. Curr Drug Targets 2011; 12(8): 1202-15.
[http://dx.doi.org/10.2174/138945011795906543] [PMID: 21561415]
[29]
DeGeer J, Kaplan A, Mattar P, et al. Hsc70 chaperone activity underlies Trio GEF function in axon growth and guidance induced by ne-trin-1. J Cell Biol 2015; 210(5): 817-32.
[http://dx.doi.org/10.1083/jcb.201505084] [PMID: 26323693]
[30]
Dickson BJ. Molecular mechanisms of axon guidance. Science 2002; 298(5600): 1959-64.
[http://dx.doi.org/10.1126/science.1072165] [PMID: 12471249]
[31]
Hall A, Lalli G. Rho and Ras GTPases in axon growth, guidance, and branching. Cold Spring Harb Perspect Biol 2010; 2(2): a001818.
[http://dx.doi.org/10.1101/cshperspect.a001818] [PMID: 20182621]
[32]
Boyer NP, Gupton SL. Revisiting Netrin-1: One Who Guides (Axons). Front Cell Neurosci 2018; 12: 221.
[http://dx.doi.org/10.3389/fncel.2018.00221] [PMID: 30108487]
[33]
Brouns MR, Matheson SF, Settleman J. p190 RhoGAP is the principal Src substrate in brain and regulates axon outgrowth, guidance and fasciculation. Nat Cell Biol 2001; 3(4): 361-7.
[http://dx.doi.org/10.1038/35070042] [PMID: 11283609]
[34]
Tseveleki V, Rubio R, Vamvakas SS, et al. Comparative gene expression analysis in mouse models for multiple sclerosis, Alzheimer’s disease and stroke for identifying commonly regulated and disease-specific gene changes. Genomics 2010; 96(2): 82-91.
[http://dx.doi.org/10.1016/j.ygeno.2010.04.004] [PMID: 20435134]
[35]
Chen J, Qin R. MicroRNA 138 5p regulates the development of spinal cord injury by targeting SIRT1. Mol Med Rep 2020; 22(1): 328-36.
[http://dx.doi.org/10.3892/mmr.2020.11071] [PMID: 32319664]
[36]
Wang Y, Han T, Guo R, et al. Micro-RNA let-7a-5p derived from mesenchymal stem cell-derived extracellular vesicles promotes the re-growth of neurons in spinal-cord-injured rats by targeting the HMGA2/SMAD2 axis. Front Mol Neurosci 2022; 15: 850364.
[http://dx.doi.org/10.3389/fnmol.2022.850364] [PMID: 35401112]
[37]
Li F, Zhang L, Xue H, Xuan J, Rong S, Wang K. SIRT1 alleviates hepatic ischemia-reperfusion injury via the miR-182-mediated XBP1/NLRP3 pathway. Mol Ther Nucleic Acids 2021; 23: 1066-77.
[http://dx.doi.org/10.1016/j.omtn.2020.11.015] [PMID: 33664991]
[38]
Bai Y, Wang J, Chen Y, et al. The miR-182/Myadm axis regulates hypoxia-induced pulmonary hypertension by balancing the BMP- and TGF-β-signalling pathways in an SMC/EC-crosstalk-associated manner. Basic Res Cardiol 2021; 116(1): 53.
[http://dx.doi.org/10.1007/s00395-021-00892-6] [PMID: 34546460]
[39]
Tu YK, Hsueh YH, Huang HC. Human olfactory ensheathing cell-derived extracellular cesicles: miRNA profile and neuroprotective effect. Curr Neurovasc Res 2021; 18(4): 395-408.
[http://dx.doi.org/10.2174/1567202618666211012162111] [PMID: 34645375]
[40]
Lu P, Woodruff G, Wang Y, et al. Long-distance axonal growth from human induced pluripotent stem cells after spinal cord injury. Neuron 2014; 83(4): 789-96.
[http://dx.doi.org/10.1016/j.neuron.2014.07.014] [PMID: 25123310]
[41]
Kadoya K, Lu P, Nguyen K, et al. Spinal cord reconstitution with homologous neural grafts enables robust corticospinal regeneration. Nat Med 2016; 22(5): 479-87.
[http://dx.doi.org/10.1038/nm.4066] [PMID: 27019328]
[42]
Xia B, Gao J, Li S, et al. Extracellular vesicles derived from olfactory ensheathing cells promote peripheral nerve regeneration in rats. Front Cell Neurosci 2019; 13: 548.
[http://dx.doi.org/10.3389/fncel.2019.00548] [PMID: 31866834]

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