Human Bone Marrow Mesenchymal Stem Cells-derived Exosomal miRNA-21-5p Inhibits Lidocaine-induced Apoptosis in SH-SY5Y Neuroblastoma Cells
-
Chao Chen
,
Feiyu Zhu
,
Feifan Liu
,
Yufeng Yao
,
Zhihong Ma
,
Shanhong Luo
Abstract
Background: Local anesthetic lidocaine is one of the most common pain therapies, but high concentration of lidocaine induced neurotoxicity and its mechanism is unclear. Exosomal microRNAs (miRNAs) is implicated in neuronal diseases, but its role in lidocaine induced neurotoxicity remains to be elucidated.
Methods: All the experiments were performed at Huzhou Key Laboratory of Molecular Medicine, Huzhou City, Jiangsu Province, China in 2022. Lidocaine was used to induce apoptosis of SH-SY5Y cells. Exosomes isolated from bone marrow mesenchymal stem cells (BMSC-exos) were used to co-treat SH-SY5Y cells with lidocaine. Cell apoptosis was measured using a flow cytometer. PKH-67 Dye was used for exosome uptake assay. miR-21-5p mimics/inhibitors, or negative controls were transfected with Lipo2000 to study its effect on lid-induced injury. Interactions between miR-21-5p and PDCD4 was analyzed by luciferase reporter assay.
Results: Administration of BMSC-exo protected SH-SY5Y cells against lidocaine induced apoptosis. Suppressing miR-21-5p dramatically enhanced PDCD4, but miR-21-5p overexpression sharply down-regulated PDCD4. Mechanism study showed that miR-21-5p bound to 3’-UTR of PDCD4 to inhibit it. Suppressing miR-21-5p reversed the effect of BMSC-exo on Lid-induced injury. Results also indicate that miR-21-5p regulated lidocaine-induced injury through targeting PDCD4.
Conclusion: BMSC-exos protected SH-SY5Y cells against lidocaine induced apoptosis through miR-21-5p by targeting PDCD4, which may develop new strategy in the management of lidocaine-induced neurotoxicity.
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30. Chan JK, Blansit K, Kiet T, et al (2014). The inhibition of miR-21 promotes apoptosis and chemosensitivity in ovarian cancer. Gynecol Oncol, 132(3):739-44.
31. Li D, Huang S, Zhu J, et al (2019). Exo-somes from MiR-21-5p-Increased Neu-rons Play a Role in Neuroprotection by Suppressing Rab11a-Mediated Neuronal Autophagy In Vitro After Traumatic Brain Injury. Med Sci Monit, 25:1871-1885.
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33. Yelamanchili SV, Lamberty BG, Rennard DA, et al (2015). MiR-21 in Extracellular Vesicles Leads to Neurotoxicity via TLR7 Signaling in SIV Neurological Disease. PLoS Pathog, 11(7):e1005032.
34. Oliveto S, Mancino M, Manfrini N, et al (2017). Role of microRNAs in translation regulation and cancer. World J Biol Chem, 8(1):45-56.
35. Xu P, Wu Q, Yu J, et al (2020). A Systematic Way to Infer the Regulation Relations of miRNAs on Target Genes and Critical miRNAs in Cancers. Front Genet, 11:278.
36. Li Q, Li B, Li Q, et al (2018). Exosomal miR-21-5p derived from gastric cancer promotes peritoneal metastasis via meso-thelial-to-mesenchymal transition. Cell Death Dis, 9(9):854.
37. Liu Z, Yu M, Fei B, et al (2018). miR‑21‑5p targets PDHA1 to regulate glycolysis and cancer progression in gastric cancer. Oncol Rep, 40(5):2955-2963.
38. Wan J, Yang J, Huang Y, et al (2018). Mi-croRNA-150 inhibitors enhance cell apoptosis of melanoma by targeting PDCD4. Oncol Lett, 15(2):1475-1482.
39. Wang Y, Liu Z, Shen J (2019). MicroRNA-421-targeted PDCD4 regulates breast cancer cell proliferation. Int J Mol Med, 43(1):267-275.
40. Guo J, Ozaki I, Xia J, et al (2019). PDCD4 Knockdown Induces Senescence in He-patoma Cells by Up-Regulating the p21 Expression. Front Oncol, 8:661.
41. Gao X, Huang X, Yang Q, et al (2021). Mi-croRNA-21-5p targets PDCD4 to modu-late apoptosis and inflammatory re-sponse to Clostridium perfringens beta2 toxin infection in IPEC-J2 cells. Dev Comp Immunol, 114:103849.
2. Anderson T (2016). Doctors lobby for bet-ter chronic pain management. Lancet, 388(10062):2856-2858.
3. Kuehn B (2018). Chronic Pain Prevalence. JAMA, 320(16):1632.
4. Tikhonov DB, Zhorov BS (2017). Mecha-nism of sodium channel block by local anesthetics, antiarrhythmics, and anticon-vulsants. J Gen Physiol, 149(4):465-481.
5. Donaldson M, Goodchild JH (2018). Lido-caine turns 70: the evolution of dental lo-cal anesthesia. Gen Dent, 66(3):6-9.
6. Karm MH, Park FD, Kang M, et al (2017). Comparison of the efficacy and safety of 2% lidocaine HCl with different epineph-rine concentration for local anesthesia in participants undergoing surgical extrac-tion of impacted mandibular third mo-lars: A multicenter, randomized, double-blind, crossover, phase IV trial. Medicine (Baltimore), 96(21):e6753.
7. Kim DD, Asif A, Kataria S (2016). Presenta-tion of Neurolytic Effect of 10% Lido-caine after Perineural Ultrasound Guided Injection of a Canine Sciatic Nerve: A Pi-lot Study. Korean J Pain, 29(3):158-63.
8. Bianco P (2014). "Mesenchymal" stem cells. Annu Rev Cell Dev Biol, 30:677-704.
9. Futrega K, Mosaad E, Chambers K, et al (2018). Bone marrow-derived stem/stromal cells (BMSC) 3D microtis-sues cultured in BMP-2 supplemented osteogenic induction medium are prone to adipogenesis. Cell Tissue Res, 374(3):541-553.
10. Wu J, Zhang W, Ran Q, et al (2018). The Differentiation Balance of Bone Marrow Mesenchymal Stem Cells Is Crucial to Hematopoiesis. Stem Cells Int, 2018:1540148.
11. Wislet-Gendebien S, Laudet E, Neirinckx V, et al (2012). Mesenchymal stem cells and neural crest stem cells from adult bone marrow: characterization of their surpris-ing similarities and differences. Cell Mol Life Sci, 69(15):2593-608.
12. Hao J, Li S, Shi X, et al (2018). Bone mar-row mesenchymal stem cells protect against n-hexane-induced neuropathy through beclin 1-independent inhibition of autophagy. Sci Rep, 8(1):4516.
13. Baglio SR, Rooijers K, Koppers-Lalic D, et al (2015). Human bone marrow- and adi-pose-mesenchymal stem cells secrete ex-osomes enriched in distinctive miRNA and tRNA species. Stem Cell Res Ther, 6(1):127.
14. Ruivo CF, Adem B, Silva M, et al (2017). The Biology of Cancer Exosomes: In-sights and New Perspectives. Cancer Res, 77(23):6480-6488.
15. Beyer C, Zampetaki A, Lin NY, et al (2015). Signature of circulating microRNAs in osteoarthritis. Ann Rheum Dis, 74(3):e18.
16. Zhou W, Fong MY, Min Y, et al (2014). Cancer-secreted miR-105 destroys vascu-lar endothelial barriers to promote metas-tasis. Cancer Cell, 25(4):501-15.
17. Zhuang G, Wu X, Jiang Z, et al (2012). Tu-mour-secreted miR-9 promotes endothe-lial cell migration and angiogenesis by ac-tivating the JAK-STAT pathway. EMBO J, 31(17):3513-23.
18. Gaudelot K, Gibier JB, Pottier N, et al (2017). Targeting miR-21 decreases ex-pression of multi-drug resistant genes and promotes chemosensitivity of renal carcinoma. Tumour Biol, 39(7):1010428317707372.
19. Zhao Y, Zhao L, Ischenko I, et al (2015). Antisense inhibition of microRNA-21 and microRNA-221 in tumor-initiating stem-like cells modulates tumorigenesis, metastasis, and chemotherapy resistance in pancreatic cancer. Target Oncol, 10(4):535-48.
20. Gao X, Xiong Y, Li Q, et al (2020). Extra-cellular vesicle-mediated transfer of miR-21-5p from mesenchymal stromal cells to neurons alleviates early brain injury to improve cognitive function via the PTEN/Akt pathway after subarachnoid hemorrhage. Cell Death Dis, 11(5):363.
21. Fu X, He Y, Wang X, et al (2017). Overex-pression of miR-21 in stem cells im-proves ovarian structure and function in rats with chemotherapy-induced ovarian damage by targeting PDCD4 and PTEN to inhibit granulosa cell apoptosis. Stem Cell Res Ther, 8(1):187.
22. Théry C, Amigorena S, Raposo G, et al (2006). Isolation and characterization of exosomes from cell culture supernatants and biological fluids. Curr Protoc Cell Biol, 3:Unit 3.22.
23. Jensen EC (2012). The basics of western blotting. Anat Rec (Hoboken), 295:369-371.
24. Bas-Orth C, Koch M, Lau D, et al (2020). A microRNA signature of toxic extrasynap-tic N-methyl-D-aspartate (NMDA) re-ceptor signaling. Molecular Brain, 13(1):3.
25. Yin KJ, Deng Z, Huang H, et al (2010). miR-497 regulates neuronal death in mouse brain after transient focal cerebral ischemia. Neurobiol Dis, 38(1):17-26.
26. Di Pietro V, Ragusa M, Davies D, et al (2017). MicroRNAs as Novel Biomarkers for the Diagnosis and Prognosis of Mild and Severe Traumatic Brain Injury. J Neu-rotrauma, 34(11):1948-1956.
27. Wang N, Qiu P, Cui W, et al (2019). Recent Advances in Multi-target Anti-Alzheimer Disease Compounds (2013 Up to the Present). Curr Med Chem, 26(30):5684-5710.
28. Singh R, Letai A, Sarosiek K (2019). Regula-tion of apoptosis in health and disease: the balancing act of BCL-2 family pro-teins. Nat Rev Mol Cell Biol, 20(3):175-193.
29. Xu X, Lai Y, Hua ZC (2019). Apoptosis and apoptotic body: disease message and therapeutic target potentials. Biosci Rep, 39(1):BSR20180992.
30. Chan JK, Blansit K, Kiet T, et al (2014). The inhibition of miR-21 promotes apoptosis and chemosensitivity in ovarian cancer. Gynecol Oncol, 132(3):739-44.
31. Li D, Huang S, Zhu J, et al (2019). Exo-somes from MiR-21-5p-Increased Neu-rons Play a Role in Neuroprotection by Suppressing Rab11a-Mediated Neuronal Autophagy In Vitro After Traumatic Brain Injury. Med Sci Monit, 25:1871-1885.
32. Buller B, Liu X, Wang X, et al (2010). Mi-croRNA-21 protects neurons from is-chemic death. FEBS J, 277(20):4299-307.
33. Yelamanchili SV, Lamberty BG, Rennard DA, et al (2015). MiR-21 in Extracellular Vesicles Leads to Neurotoxicity via TLR7 Signaling in SIV Neurological Disease. PLoS Pathog, 11(7):e1005032.
34. Oliveto S, Mancino M, Manfrini N, et al (2017). Role of microRNAs in translation regulation and cancer. World J Biol Chem, 8(1):45-56.
35. Xu P, Wu Q, Yu J, et al (2020). A Systematic Way to Infer the Regulation Relations of miRNAs on Target Genes and Critical miRNAs in Cancers. Front Genet, 11:278.
36. Li Q, Li B, Li Q, et al (2018). Exosomal miR-21-5p derived from gastric cancer promotes peritoneal metastasis via meso-thelial-to-mesenchymal transition. Cell Death Dis, 9(9):854.
37. Liu Z, Yu M, Fei B, et al (2018). miR‑21‑5p targets PDHA1 to regulate glycolysis and cancer progression in gastric cancer. Oncol Rep, 40(5):2955-2963.
38. Wan J, Yang J, Huang Y, et al (2018). Mi-croRNA-150 inhibitors enhance cell apoptosis of melanoma by targeting PDCD4. Oncol Lett, 15(2):1475-1482.
39. Wang Y, Liu Z, Shen J (2019). MicroRNA-421-targeted PDCD4 regulates breast cancer cell proliferation. Int J Mol Med, 43(1):267-275.
40. Guo J, Ozaki I, Xia J, et al (2019). PDCD4 Knockdown Induces Senescence in He-patoma Cells by Up-Regulating the p21 Expression. Front Oncol, 8:661.
41. Gao X, Huang X, Yang Q, et al (2021). Mi-croRNA-21-5p targets PDCD4 to modu-late apoptosis and inflammatory re-sponse to Clostridium perfringens beta2 toxin infection in IPEC-J2 cells. Dev Comp Immunol, 114:103849.
| Files | ||
| Issue | Vol 52 No 4 (2023) | |
| Section | Original Article(s) | |
| DOI | https://doi.org/10.18502/ijph.v52i4.12446 | |
| Keywords | ||
| Microrna Exosomes Lidocaine Programmed cell death protein 4 (PDCD4) Apoptosis Neuronal toxicity | ||
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This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License. |
How to Cite
1.
Chen C, Zhu F, Liu F, Yao Y, Ma Z, Luo S. Human Bone Marrow Mesenchymal Stem Cells-derived Exosomal miRNA-21-5p Inhibits Lidocaine-induced Apoptosis in SH-SY5Y Neuroblastoma Cells. Iran J Public Health. 2023;52(4):756-765.
