Hepatocyte growth factor promotes neuroinflammation mediated by BV2 cells through activating NF-κB signaling pathway

doi:10.13418/j.issn.1001-165x.2024.6.10

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Chinese Journal of Clinical Anatomy ›› 2024, Vol. 42 ›› Issue (6) : 666-672. DOI: 10.13418/j.issn.1001-165x.2024.6.10

Hepatocyte growth factor promotes neuroinflammation mediated by BV2 cells through activating NF-κB signaling pathway

Shen Ruoqi, Lu Yubao, Wang Ziming, Liu Bin, Zhang Liangming*, Yang Yang*

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Abstract

Objective To explore the effect of hepatocyte growth factor (HGF) on microglia-mediated neuroinflammation and its regulatory mechanism, and to provide experimental basis and theoretical reference for the determination of possible treatment targets. Methods The mouse immortalized cell line-BV2 cells, which retain multiple morphological and functional characteristics of microglia, were divided into a control group and a HGF group. The effects of HGF on the activity of NF-κB signaling pathway and subsequent expression of neuroinflammatory factors were determined by tyrosine phosphorylated proteomic analysis, cell survival assay, quantitative real time polymerase chain reaction (qRT-PCR) and western blot (WB). Results Tyrosine phosphorylated proteomic analysis showed that after addition of HGF, NF-κB signaling was one of the most enriched pathways in BV2 cells. At 1 hour after the addition of HGF with different concentrations, the proliferation activity of BV2 cells was decreased. At both 6 hours and 12 hours after the supplementation of HGF with various concentrations, the proliferation activity of BV2 cells increased at early stage, while decreased at late stage. qRT-PCR found that HGF could upregulate the transcription level of inflammatory factors derived from BV2 cells (iNOS, TNF-α, IL-1β). WB also showed that HGF could promote protein translation of associated inflammatory factors (TNF-α, NF-κB p65). Conclusions This study confirms the role of HGF in promoting neuroinflammation by activating the NF-κB signaling pathway in BV2 cells and its mechanism. It provides important clues to further explore the regulatory strategies on neuroinflammation to develop more effective treatment in the clinic.

Key words

Hepatocyte growth factor; / / Microglia; / / Neuroinflammation; / / NF-κB signaling pathway / Factor

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Shen Ruoqi, Lu Yubao, Wang Ziming, Liu Bin, Zhang Liangming, Yang Yang. Hepatocyte growth factor promotes neuroinflammation mediated by BV2 cells through activating NF-κB signaling pathway[J]. Chinese Journal of Clinical Anatomy. 2024, 42(6): 666-672 https://doi.org/10.13418/j.issn.1001-165x.2024.6.10

References

[1] Harry GJ. Microglia during development and aging [J]. Pharmacol Ther, 2013, 139(3): 313-326. DOI: 10.1016/j.pharmthera.2013.04.013.
[2] Liddelow SA, Guttenplan KA, Clarke LE, et al. Neurotoxic reactive astrocytes are induced by activated microglia [J]. Nature, 2017, 541(7638): 481-487. DOI: 10.1038/nature21029.
[3] Zhang ZS, Yang RH, Yao X, et al. HGF/c-MET pathway contributes to cisplatin-mediated PD-L1 expression in hepatocellular carcinoma [J]. Cell Biol Int, 2021, 45(12): 2521-2533. DOI: 10.1002/cbin.11697.
[4] Shen Z, Xue W, Zheng Y, et al. Molecular mechanism study of HGF/c-MET pathway activation and immune regulation for a tumor diagnosis model [J]. Cancer Cell Int, 2021, 21(1): 374. DOI: 10.1186/s12935-021-02051-2.
[5] Tang H, Gamdzyk M, Huang L, et al. Delayed recanalization after MCAO ameliorates ischemic stroke by inhibiting apoptosis via HGF/c-Met/STAT3/Bcl-2 pathway in rats [J]. Exp Neurol, 2020, 330: 113359. DOI: 10.1016/j.expneurol.2020.113359.
[6] Liang F, Xu X, Tu Y. Resveratrol inhibited hepatocyte apoptosis and alleviated liver fibrosis through miR-190a-5p /HGF axis [J]. Bioorg Med Chem, 2022, 57: 116593. DOI: 10.1016/j.bmc.2021.116593.
[7] Choi W, Lee J, Lee J, et al. Hepatocyte Growth Factor Regulates Macrophage Transition to the M2 Phenotype and Promotes Murine Skeletal Muscle Regeneration [J]. Front Physiol, 2019, 10: 914. DOI: 10.3389/fphys.2019.00914.
[8] Yuan S, Gong Y, Chen R, et al. Chinese herbal formula QHF inhibits hepatocellular carcinoma metastasis via HGF/c-Met signaling pathway [J]. Biomed Pharmacothe, 2020, 132: 110867. DOI: 10.1016/j.biopha.2020.110867.
[9] Yan L, He X, Tang Y, et al. HGF can reduce accumulation of inflammation and regulate glucose homeostasis in T2D mice [J]. J Physiol Biochem, 2021, 77(4): 613-624. DOI: 10.1007/s13105-021-00828-7.
[10] Rehman R, Miller M, Krishnamurthy SS, et al. Met/HGFR triggers detrimental reactive microglia in TBI [J]. Cell Rep, 2022, 41(13): 111867. DOI: 10.1016/j.celrep.2022.111867.
[11]Liao S, Wu J, Liu R, et al. A novel compound DBZ ameliorates neuroinflammation in LPS-stimulated microglia and ischemic stroke rats: Role of Akt(Ser473)/GSK3β(Ser9)-mediated Nrf2 activation [J]. Redox Biol, 2020, 36: 101644. DOI: 10.1016/j.redox.2020.101644.
[12] Zhou C, Zhang C, Chi S, et al. Effects of human marrow stromal cells on activation of microglial cells and production of inflammatory factors induced by lipopolysaccharide [J]. Brain Res, 2009, 1269: 23-30. DOI: 10.1016/j.brainres.2009.02.049.
[13] Vallarola A, Tortarolo M, De Gioia R, et al. A Novel HGF/SF Receptor (MET) Agonist Transiently Delays the Disease Progression in an Amyotrophic Lateral Sclerosis Mouse Model by Promoting Neuronal Survival and Dampening the Immune Dysregulation [J]. Int J Mol Sci, 2020, 21(22). DOI: 10.3390/ijms21228542.
[14] Pak C, Miyamoto S. A new alpha in line between KRAS and NF-κB activation? [J]. Cancer Discov, 2013, 3(6): 613-615. DOI: 10.1158/2159-8290.CD-13-0193.
[15] Mi J, Yang Y, Yao H, et al. Inhibition of heat shock protein family A member 8 attenuates spinal cord ischemia-reperfusion injury via astrocyte NF-κB/NLRP3 inflammasome pathway: HSPA8 inhibition protects spinal ischemia-reperfusion injury [J]. J Neuroinflammation, 2021, 18(1): 170. DOI: 10.1186/s12974-021-02220-0.
[16] 杨帆, 童婧涵, 李会,等. BTK抑制剂GDC-0853通过TLR4/NF-κB通路抑制M1巨噬细胞极化并改善UUO肾损伤[J]. 免疫学杂志, 2021, 37(02): 107-114. DOI: 10.13431/j.cnki.immunol.j.20210016.
[17]Weng P-W, Yadav VK, Pikatan NW, et al. Novel NFκB Inhibitor SC75741 Mitigates Chondrocyte Degradation and Prevents Activated Fibroblast Transformation by Modulating miR-21/GDF-5/SOX5 Signaling [J]. Int J Mol Sci, 2021, 22(20).11082. DOI: 10.3390/ijms222011082.
[18] Schreiber J, Jenner RG, Murray HL, et al. Coordinated binding of NF-kappaB family members in the response of human cells to lipopolysaccharide [J]. Proc Natl Acad Sci U S A, 2006, 103(15): 5899-5904. DOI.
[19] Li B, Dasgupta C, Huang L, et al. MiRNA-210 induces microglial activation and regulates microglia-mediated neuroinflammation in neonatal hypoxic-ischemic encephalopathy [J]. Cell Mol Immunol, 2020, 17(9): 976-991. DOI: 10.1038/s41423-019-0257-6.
[20] Kwon HS, Koh S-H. Neuroinflammation in neurodegenerative disorders: the roles of microglia and astrocytes [J]. Transl Neurodegener, 2020, 9(1): 42. DOI: 10.1186/s40035-020-00221-2.
[21]Liu J, Wu Y. Electro-acupuncture-modulated miR-214 prevents neuronal apoptosis by targeting Bax and inhibits sodium channel Nav1.3 expression in rats after spinal cord injury [J]. Biomed Pharmacother,2017,89:1125-1135.DOI: 10.1016/j.biopha. 2017. 02.077.
[22] Huang B, He D, Chen G, et al. α-Cyperone inhibits LPS-induced inflammation in BV-2 cells through activation of Akt/Nrf2/HO-1 and suppression of the NF-κB pathway [J]. Food Funct, 2018, 9(5): 2735-2743. DOI: 10.1039/c8fo00057c.
[23] Von Bernhardi R, Eugenín-Von Bernhardi L, Eugenín J. Microglial cell dysregulation in brain aging and neurodegeneration [J]. Front Aging Neurosci, 2015, 7: 124. DOI: 10.3389/fnagi.2015.00124.
[24] Wang X, Tang Y, Shen R, et al. Hepatocyte growth factor (HGF) optimizes oral traumatic ulcer healing of mice by reducing inflammation [J]. Cytokine, 2017, 99: 275-280. DOI: 10.1016/j.cyto.2017.08.006.