Regulation of Edaravone on TDP-43/cGAS/STING signaling in activated BV2 cells

doi:10.13418/j.issn.1001-165x.2025.5.09

PDF(8480 KB)

Chinese Journal of Clinical Anatomy ›› 2025, Vol. 43 ›› Issue (5) : 555-563. DOI: 10.13418/j.issn.1001-165x.2025.5.09

Regulation of Edaravone on TDP-43/cGAS/STING signaling in activated BV2 cells

Yang Yujia¹, Yin Qian¹, Fang Lanxi¹, Xu Dongyao¹, Duan Zhaoda², Wu Chunyun¹*, Yang Li¹*

Author information +

History +

Abstract

Objective To explore the effect of Edaravone on TDP-43/cGAS/STING signaling in lipopolysaccharide-activated BV2 microglia. Methods The SwissTargetPrediction, Superpred and TargetNet access to potential targets of Edaravone, the GeneCards, OMIM and TTD databases selected neuroinflammation related genes, get both intersection targets. The protein interaction network was constructed using STRING database and Cytoscape software. GO functional enrichment and KEGG pathway enrichment were analyzed using Metascape database. BV2 microglia were divided into control group, lipopolysaccharide activated group and lipopolysaccharide plus Edaravone group. The expression changes of TDP-43, cGAS, STING, TNF-α and IL-1β were detected by western blot and immunofluorescence staining. Results Network pharmacology identified 70 potential targets of Edaravone in regulating neuroinflammation, with 1339 GO and 157 KEGG pathways enriched. Western blot and immunofluorescence staining showed that, compared with the control group, the expression of TDP-43, cGAS and STING, as well as inflammatory factors TNF-α and IL-1β were increased in activated BV2 microglia, while the expressions of these factors were decreased after Edaravone intervention. Conclusions Edaravone can inhibit TDP-43/cGAS/STING signaling in BV2 cells to reduce inflammation.

Key words

Edaravone; / TDP-43; / cGAS; / / STING; / Neuroinflammations; / Network pharmacology

Cite this article

EndNote

Ris (Procite)

Bibtex

Download Citations

Yang Yujia, Yin Qian, Fang Lanxi, Xu Dongyao, Duan Zhaoda, Wu Chunyun, Yang Li. Regulation of Edaravone on TDP-43/cGAS/STING signaling in activated BV2 cells[J]. Chinese Journal of Clinical Anatomy. 2025, 43(5): 555-563 https://doi.org/10.13418/j.issn.1001-165x.2025.5.09

References

[1] Alsbrook DL, Di Napoli M, Bhatia K, et al. Neuroinflammation in Acute Ischemic and Hemorrhagic Stroke [J]. Curr Neurol Neurosci Rep, 2023, 23(8): 407-431. DOI: 10.1007/s11910-023-01282-2.
[2] Planas AM. Role of microglia in stroke [J]. Glia, 2024, 72(6): 1016-1053. DOI: 10.1002/glia.24501.
[3] Yuan Y, Zha H, Rangarajan P, et al. Anti-inflammatory effects of Edaravone and Scutellarin in activated microglia in experimentally induced ischemia injury in rats and in BV-2 microglia [J]. BMC Neurosci, 2014, 15: 125. DOI: 10.1186/s12868-014-0125-3.
[4] Li X, Liu Z, Liao J, et al. Network pharmacology approaches for research of Traditional Chinese Medicines [J]. Chin J Nat Med, 2023, 21(5): 323-332. DOI: 10.1016/S1875-5364(23)60429-7.
[5] 王子怡, 王鑫, 张岱岩, 等. 中医药网络药理学:《指南》引领下的新时代发展[J]. 中国中药杂志, 2022, 47(1): 7-17. DOI: 10.19540/j.cnki.cjcmm.20210914.702.
Wang ZY, Wang X, Zhang DY, et al. Traditional Chinese medicine network pharmacology: development in new era under guidance of network pharmacology evaluation method guidance[J]. China Journal of Chinese Materia Media, 2022, 47(1): 7-17. DOI: 10.19540/j.cnki.cjcmm.20210914.702.
[6] Yu CH, Davidson S, Harapas CR, et al. TDP-43 Triggers Mitochondrial DNA Release via mPTP to Activate cGAS/STING in ALS [J]. Cell, 2020, 183(3): 636-649. DOI: 10.1016/j.cell.2020.09.020.
[7] Lloyd AF, Davies CL, Miron VE. Microglia: origins, homeostasis, and roles in myelin repair [J]. Curr Opin Neurobiol, 2017, 47: 113-120. DOI: 10.1016/j.conb.2017.10.001.
[8] Colonna M, Butovsky O. Microglia Function in the Central Nervous System During Health and Neurodegeneration [J]. Annu Rev Immunol, 2017, 35: 441-468. DOI: 10.1146/annurev-immunol-051116-052358.
[9] Jurcau A, Simion A. Neuroinflammation in Cerebral Ischemia and Ischemia/Reperfusion Injuries: From Pathophysiology to Therapeutic Strategies [J]. Int J Mol Sci, 2021, 23(1):14. DOI: 10.3390/ijms 23010014.
[10]Stuckey SM, Ong LK, Collins-Praino LE, et al. Neuroinflammation as a Key Driver of Secondary Neurodegeneration Following Stroke? [J]. Int J Mol Sci, 2021, 22(23):13101. DOI: 10.3390/ijms222313101.
[11]Fidalgo M, Ricardo Pires J, Viseu I, et al. Edaravone for acute ischemic stroke - Systematic review with meta-analysis [J]. Clin Neurol Neurosurg, 2022, 219: 107299. DOI: 10.1016/j.clineuro.2022.107299.
[12]Abe K, Itoyama Y, Sobue G, et al. Confirmatory double-blind, parallel-group, placebo-controlled study of efficacy and safety of edaravone (MCI-186) in amyotrophic lateral sclerosis patients [J]. Amyotroph Lateral Scler Frontotemporal Degener, 2014, 15(7-8): 610-617. DOI: 10.3109/21678421.2014.959024.
[13]Li J, Dai X, Zhou L, et al. Edaravone Plays Protective Effects on LPS-Induced Microglia by Switching M1/M2 Phenotypes and Regulating NLRP3 Inflammasome Activation [J]. Front Pharmacol, 2021, 12: 691773. DOI: 10.3389/fphar.2021.691773.
[14]祁志, 杨力, 贾秋叶, 等. 依达拉奉经MAPKs通路对脂多糖激活的小胶质细胞Sirt3表达调控 [J]. 中国临床解剖学杂志, 2024, 42(01): 47-53. DOI: 10.13418/j.issn.1001-165x.2024.1.09.
Qi Z, Yang L, Jia QY, et al. Edaravone regulates Sirt3 expression in lipopolysaccharide-activated microglia via MAPKs signaling pathway[J]. Chinese Journal of Clinical Anatomy, 2024, 42(01): 47-53. DOI: 10.13418/j.issn.1001-165x.2024.1.09.
[15]Xiaoying M, Zhiming H, Tao Y, et al. Elucidating the molecular mechanisms underlying anti-inflammatory effects of Morchella esculenta in the arachidonic acid metabolic pathway by network pharmacology and molecular docking [J]. Sci Rep, 2023, 13(1): 15881. DOI: 10.1038/s41598-023-42658-1.
[16]Hu P, Sun N, Khan A, et al. Network pharmacology-based study on the mechanism of scutellarin against zearalenone-induced ovarian granulosa cell injury [J]. Ecotoxicol Environ Saf, 2021, 227: 112865. DOI: 10.1016/j.ecoenv.2021.112865.
[17]Ho DM, Shaban M, Mahmood F, et al. cAMP/PKA signaling regulates TDP-43 aggregation and mislocalization [J]. Proc Natl Acad Sci U S A, 2024, 121(24): e2400732121. DOI: 10.1073/pnas.2400732121.
[18]Pérez-Berlanga M, Wiersma VI, Zbinden A, et al. Loss of TDP-43 oligomerization or RNA binding elicits distinct aggregation patterns [J]. Embo J, 2023, 42(17): e111719. DOI: 10.15252/embj.2022111719.
[19]Arseni D, Hasegawa M, Murzin AG, et al. Structure of pathological TDP-43 filaments from ALS with FTLD [J]. Nature, 2022, 601(7891): 139-143. DOI: 10.1038/s41586-021-04199-3.
[20]Maekawa H, Inoue T, Ouchi H, et al. Mitochondrial Damage Causes Inflammation via cGAS-STING Signaling in Acute Kidney Injury [J]. Cell Rep, 2019, 29(5): 1261-1273. DOI: 10.1016/j.celrep.2019.09.050.
[21] Decout A, Katz JD, Venkatraman S, et al. The cGAS-STING pathway as a therapeutic target in inflammatory diseases [J]. Nat Rev Immunol, 2021, 21(9): 548-569. DOI: 10.1038/s41577-021-00524-z.
[22] Zou M, Ke Q, Nie Q, et al. Inhibition of cGAS-STING by JQ1 alleviates oxidative stress-induced retina inflammation and degeneration [J]. Cell Death Differ, 2022, 29(9): 1816-1833. DOI: 10.1038/s41418-022-00967-4.
[23] Shao J, Meng Y, Yuan K, et al. RU.521 mitigates subarachnoid hemorrhage-induced brain injury via regulating microglial polarization and neuroinflammation mediated by the cGAS/STING/NF-κB pathway [J]. Cell Commun Signal, 2023, 21(1): 264. DOI: 10.1186/s12964-023-01274-2.