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Volume 21, Issue 3
  • ISSN: 1567-2026
  • E-ISSN: 1875-5739

Abstract

Background

CI/R, characterized by ischemic injury following abrupt reestablishment of blood flow, can cause oxidative stress, mitochondrial dysfunction, and apoptosis. We used oxygen-glucose deprivation/reoxygenation (OGD/R) induced injury in HT22 and primary mouse cortical neurons (MCN) as a model for CI/R.

Objective

This study investigates the role of miR-188-5p in hippocampal neuron cell injury associated with Cerebral Ischemia-Reperfusion (CI/R).

Methods

HT22 and MCN cells were induced by OGD/R to construct an model of CI/R. Cell apoptosis and proliferation were assessed using flow cytometry and the Cell Counting Kit-8 (CCK8). ELISA was conducted to measure the levels of IL-1β, IL-6, and TNF-α. Moreover, the interaction between miR-188-5p and IL6ST was investigated using dual luciferase assay, the expression of miR-188-5p, Bax, cleaved-caspase3, IL-6, Bcl-2, IL-1β, TNF-α, IL6ST, NFκB, NLRP3 and STAT3 was evaluated using RT-qPCR or Western blot, and immunofluorescence was used to analyze the co-expression of p-STAT3 and NLRP3 in neuronal cells.

Results

OGD/R reduced proliferation and miR-188-5p levels and increased IL6ST expression, inflammation, and apoptosis in HT22 and MCN cells. Moreover, miR-188-5p was found to bind to IL6ST. Mimics of miR-188-5p reduced apoptosis, lowered the expression of cleaved-caspase3 and Bax proteins, and elevated Bcl-2 protein expression in cells treated with OGD/R. Overexpression of miR-188-5p decreased the levels of NLRP3 and p-STAT3 in the OGD/R group. Furthermore, the overexpression of miR-188-5p reduced IL6ST, p-NFκB/NFκB, p-STAT3/STAT3, and NLRP3 proteins in OGD/R, and these effects could be reversed by IL6ST overexpression.

Conclusion

Mimics of miR-188-5p were found to inhibit inflammation and the STAT3/NLRP3 pathway IL6ST, thereby ameliorating injury in HT22 and MCN cells treated with OGD/R in the context of CI/R.

© 2024 Bentham Science Publishers
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2024-05-22
2025-01-15

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References

  1. LinS.P. YeS. LongY. Circular RNA expression alterations are involved in OGD/R-induced neuron injury.Biochem. Biophys. Res. Commun.20164711525610.1016/j.bbrc.2016.01.183 26845359
     [Google Scholar]
  2. Ghafouri-FardS. ShooreiH. TaheriM. Non-coding RNAs participate in the ischemia-reperfusion injury.Biomed. Pharmacother.202012911041910.1016/j.biopha.2020.110419 32563988
     [Google Scholar]
  3. XingF. LiuY. DongR. ChengY. miR-374 improves cerebral ischemia reperfusion injury by targeting Wnt5a.Exp. Anim.202170112613610.1538/expanim.20‑0034 33116025
     [Google Scholar]
  4. ZhangY. DingN. YiH. Identification of differentially expressed miRNA 48 h after cerebral ischemia–reperfusion injury in mice by the technique of miRNA microarray.Can. J. Physiol. Pharmacol.2020981285586010.1139/cjpp‑2019‑0701 32516555
     [Google Scholar]
  5. TianT. CaoL. HeC. Targeted delivery of neural progenitor cell-derived extracellular vesicles for anti-inflammation after cerebral ischemia.Theranostics202111136507652110.7150/thno.56367 33995671
     [Google Scholar]
  6. WangY. XiaoG. HeS. Protection against acute cerebral ischemia/reperfusion injury by QiShenYiQi via neuroinflammatory network mobilization.Biomed. Pharmacother.202012510994510.1016/j.biopha.2020.109945 32028240
     [Google Scholar]
  7. WuR. LiX. XuP. TREM2 protects against cerebral ischemia/reperfusion injury.Mol. Brain20171012010.1186/s13041‑017‑0296‑9 28592261
     [Google Scholar]
  8. LiuH. WuX. LuoJ. Pterostilbene attenuates astrocytic inflammation and neuronal oxidative injury after ischemia-reperfusion by inhibiting NF-κB phosphorylation.Front. Immunol.201910240810.3389/fimmu.2019.02408 31681297
     [Google Scholar]
  9. DongX. WangL. SongG. Physcion protects rats against cerebral ischemia-reperfusion injury via inhibition of TLR4/NF-kB signaling pathway.Drug Des. Devel. Ther.20211527728710.2147/DDDT.S267856 33536742
     [Google Scholar]
  10. SuzukiS. TanakaK. SuzukiN. Ambivalent aspects of interleukin-6 in cerebral ischemia: inflammatory versus neurotrophic aspects.J. Cereb. Blood Flow Metab.200929346447910.1038/jcbfm.2008.141 19018268
     [Google Scholar]
  11. JungJ.E. KimG.S. ChanP.H. Neuroprotection by interleukin-6 is mediated by signal transducer and activator of transcription 3 and antioxidative signaling in ischemic stroke.Stroke201142123574357910.1161/STROKEAHA.111.626648 21940958
     [Google Scholar]
  12. LuoC. LiB. ChenL. ZhaoL. WeiY. IL-27 protects the brain from ischemia-reperfusion injury via the gp130/STAT3 signaling pathway.J. Mol. Neurosci.20217191838184810.1007/s12031‑021‑01802‑0 33851350
     [Google Scholar]
  13. GongZ. PanJ. ShenQ. LiM. PengY. Mitochondrial dysfunction induces NLRP3 inflammasome activation during cerebral ischemia/reperfusion injury.J. Neuroinflammation201815124210.1186/s12974‑018‑1282‑6 30153825
     [Google Scholar]
  14. JiangQ. TangG. ZhongX.M. DingD.R. WangH. LiJ.N. Role of Stat3 in NLRP3/caspase‐1‐mediated hippocampal neuronal pyroptosis in epileptic mice.Synapse20217512e2222110.1002/syn.22221 34958692
     [Google Scholar]
  15. WangM. ZhangH. YangF. miR‐188‐5p suppresses cellular proliferation and migration via IL6ST: A potential noninvasive diagnostic biomarker for breast cancer.J. Cell. Physiol.202023554890490110.1002/jcp.29367 31650530
     [Google Scholar]
  16. YanX. YuA. ZhengH. WangS. HeY. WangL. Calycosin-7- O - β - D -glucoside Attenuates OGD/R-induced damage by preventing oxidative stress and neuronal apoptosis via the SIRT1/FOXO1/PGC-1 α pathway in HT22 cells.Neural Plast.2019201911110.1155/2019/8798069 31885537
     [Google Scholar]
  17. YuanY. ZhaiY. ChenJ. XuX. WangH. Kaempferol ameliorates oxygen-glucose deprivation/reoxygenation-induced neuronal ferroptosis by activating Nrf2/SLC7A11/GPX4 axis.Biomolecules202111792310.3390/biom11070923 34206421
     [Google Scholar]
  18. DengZ. OuH. RenF. LncRNA SNHG14 promotes OGD/R-induced neuron injury by inducing excessive mitophagy via miR-182-5p/BINP3 axis in HT22 mouse hippocampal neuronal cells.Biol. Res.20205313810.1186/s40659‑020‑00304‑4 32912324
     [Google Scholar]
  19. FanZ.X. YangJ. The role of microRNAs in regulating myocardial ischemia reperfusion injury.Saudi Med. J.201536778779310.15537/smj.2015.7.11089 26108581
     [Google Scholar]
  20. LiuJ. LiL. SuoW.Z. HT22 hippocampal neuronal cell line possesses functional cholinergic properties.Life Sci.2009849-1026727110.1016/j.lfs.2008.12.008 19135458
     [Google Scholar]
  21. Materna-KirylukA. PollakA. GawalskiK. Mosaic IL6ST variant inducing constitutive GP130 cytokine receptor signaling as a cause of neonatal onset immunodeficiency with autoinflammation and dysmorphy.Hum. Mol. Genet.2021303-422623310.1093/hmg/ddab035 33517393
     [Google Scholar]
  22. ZhangL. CaiQ. LinS. Qingda granule exerts neuroprotective effects against ischemia/reperfusion-induced cerebral injury via lncRNA GAS5/miR-137 signaling pathway.Int. J. Med. Sci.20211871687169810.7150/ijms.53603 33746585
     [Google Scholar]
  23. ZhouY. YangL. BoC. ZhangX. ZhangJ. LiY. MicroRNA-9-3p aggravates cerebral ischemia/reperfusion injury by targeting fibroblast growth factor 19 (FGF19) to inactivate GSK-3β/Nrf2/ARE signaling.Neuropsychiatr. Dis. Treat.2021171989200210.2147/NDT.S290237 34177264
     [Google Scholar]
  24. LiW. ZhuQ. XuX. HuX. MiR-27a-3p suppresses cerebral ischemia-reperfusion injury by targeting FOXO1.Aging2021138117271173710.18632/aging.202866 33875617
     [Google Scholar]
  25. ZhangM. ZhuY. WeiM. LiuH. Neuroprotective effects of miR-30c on rats with cerebral ischemia/reperfusion injury by targeting SOX9.Pathol. Res. Pract.20202161215327110.1016/j.prp.2020.153271 33161310
     [Google Scholar]
  26. WangW. HuY. ZhangY. FTX attenuates cerebral ischemia–reperfusion injury by inhibiting apoptosis and oxidative stress via miR-186-5p/MDM4 pathway.Neurotox. Res.202240254255210.1007/s12640‑022‑00485‑8 35344194
     [Google Scholar]
  27. LiuY. LiY.P. XiaoL.M. Extracellular vesicles derived from M2 microglia reduce ischemic brain injury through microRNA-135a-5p/TXNIP/NLRP3 axis.Lab. Invest.2021101783785010.1038/s41374‑021‑00545‑1 33875790
     [Google Scholar]
  28. PilatiC. Zucman-RossiJ. Mutations leading to constitutive active gp130/JAK1/STAT3 pathway.Cytokine Growth Factor Rev.201526549950610.1016/j.cytogfr.2015.07.010 26188635
     [Google Scholar]
  29. HeinrichP.C. BehrmannI. Müller-NewenG. SchaperF. GraeveL. Interleukin-6-type cytokine signalling through the gp130/Jak/STAT pathway.Biochem. J.1998334Pt 2297314
     [Google Scholar]
  30. ZandersL. KnyM. HahnA. Sepsis induces interleukin 6, gp130/JAK2/STAT3, and muscle wasting.J. Cachexia Sarcopenia Muscle202213171372710.1002/jcsm.12867 34821076
     [Google Scholar]
  31. KiszałkiewiczJ.M. MajewskiS. PiotrowskiW.J. Evaluation of selected IL6/STAT3 pathway molecules and miRNA expression in chronic obstructive pulmonary disease.Sci. Rep.20211112275610.1038/s41598‑021‑01950‑8 34815425
     [Google Scholar]
  32. HuangH. ZhangG. GeZ. lncRNA MALAT1 promotes renal fibrosis in diabetic nephropathy by targeting the miR-2355-3p/IL6ST axis.Front. Pharmacol.20211264765010.3389/fphar.2021.647650 33995063
     [Google Scholar]
  33. TangM. LiuP. LiX. WangJ. ZhuX. HeF. Protective action of B1R antagonist against cerebral ischemia-reperfusion injury through suppressing miR-200c expression of Microglia-derived microvesicles.Neurol. Res.201739761262010.1080/01616412.2016.1275096 28398146
     [Google Scholar]
  34. ChenX. YaoZ. PengX. Eupafolin alleviates cerebral ischemia/reperfusion injury in rats via blocking the TLR4/NF κB signaling pathway.Mol. Med. Rep.20202265135514410.3892/mmr.2020.11637 33173992
     [Google Scholar]
  35. DengL. GuoY. LiuJ. miR-671-5p attenuates neuroinflammation via suppressing NF-κB expression in an acute ischemic stroke model.Neurochem. Res.20214671801181310.1007/s11064‑021‑03321‑1 33871800
     [Google Scholar]
  36. ChoiJ.S. KimS.Y. ChaJ.H. Upregulation of gp130 and STAT3 activation in the rat hippocampus following transient forebrain ischemia.Glia200341323724610.1002/glia.10186 12528179
     [Google Scholar]
  37. WangL. RenW. WuQ. NLRP3 inflammasome activation: A therapeutic target for cerebral ischemia–reperfusion injury.Front. Mol. Neurosci.20221584744010.3389/fnmol.2022.847440 35600078
     [Google Scholar]
  38. WangZ. LiY. YeY. NLRP3 inflammasome deficiency attenuates cerebral ischemia-reperfusion injury by inhibiting ferroptosis.Brain Res. Bull.2023193374610.1016/j.brainresbull.2022.11.016 36435361
     [Google Scholar]
  39. ZhuL. WangZ. SunX. STAT3/mitophagy axis coordinates macrophage NLRP3 inflammasome activation and inflammatory bone loss.J. Bone Miner. Res.202038233535310.1002/jbmr.4756 36502520
     [Google Scholar]
  40. ZhuH. JianZ. ZhongY. Janus kinase inhibition ameliorates ischemic stroke injury and neuroinflammation through reducing NLRP3 inflammasome activation via JAK2/STAT3 pathway inhibition.Front. Immunol.20211271494310.3389/fimmu.2021.714943 34367186
     [Google Scholar]
/content/journals/cnr/10.2174/0115672026313555240515103132
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Overexpression of MiR-188-5p Downregulates IL6ST/STAT3/NLRP3 Pathway to Ameliorate Neuron Injury in Oxygen-glucose Deprivation/Reoxygenation
Curr Neurovasc Res 21, 263 (2024); https://doi.org/10.2174/0115672026313555240515103132
/content/journals/cnr/10.2174/0115672026313555240515103132
/content/journals/cnr/10.2174/0115672026313555240515103132
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Figure S1: The membrane with markers in Western blot images.

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  • Article Type:     Research Article
Keyword(s): ameliorate neuron injury; cerebral ischemia-reperfusion; IL6ST/STAT3; inflammation; MiR-188-5p; oxygen-glucose deprivation/reoxygenation

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