XIAO Yinggang, GAO Ju. Research progress in regulation of microglial polarization by RhoA/ROCK signaling pathway[J]. Journal of Clinical Medicine in Practice, 2022, 26(20): 136-141, 148. DOI: 10.7619/jcmp.20221217
Citation: XIAO Yinggang, GAO Ju. Research progress in regulation of microglial polarization by RhoA/ROCK signaling pathway[J]. Journal of Clinical Medicine in Practice, 2022, 26(20): 136-141, 148. DOI: 10.7619/jcmp.20221217

Research progress in regulation of microglial polarization by RhoA/ROCK signaling pathway

More Information
  • Received Date: April 12, 2022
  • Available Online: November 03, 2022
  • Microglia are widely involved in various pathophysiological processes of the central nervous system, and their polarization characteristics are closely related to the inflammatory response and injury repair of neurons. Ras homologous gene family protein A (RhoA)/Rho-associated coiled-coil protein kinase (ROCK) signaling pathway plays an important role in regulating microglia polarization. At present, the related research on the treatment of neuronal damage by promoting microglial M2-type polarization has become one of the hot spots in the field of neuroscience, but the effect of RhoA/ROCK pathway on polarization is still unclear. This article reviewed the effect of RhoA/ROCK signaling pathway on microglial polarization in order to provide new ideas for the study of molecular mechanism of brain protection and clinical treatment.

  • [1]
    GUO M F, ZHANG H Y, LI Y H, et al. Fasudil inhibits the activation of microglia and astrocytes of transgenic Alzheimer′s disease mice via the downregulation of TLR4/Myd88/NF-κB pathway[J]. J Neuroimmunol, 2020, 346: 577284. doi: 10.1016/j.jneuroim.2020.577284
    [2]
    MEI B, LI J, ZUO Z Y. Dexmedetomidine attenuates Sepsis-associated inflammation and encephalopathy via central α2A adrenoceptor[J]. Brain Behav Immun, 2021, 91: 296-314. doi: 10.1016/j.bbi.2020.10.008
    [3]
    MARINO LEE S, HUDOBENKO J, MCCULLOUGH L D, et al. Microglia depletion increase brain injury after acute ischemic stroke in aged mice[J]. Exp Neurol, 2021, 336: 113530. doi: 10.1016/j.expneurol.2020.113530
    [4]
    XIONG X Y, LIU L, YANG Q W. Functions and mechanisms of microglia/macrophages in neuroinflammation and neurogenesis after stroke[J]. Prog Neurobiol, 2016, 142: 23-44. doi: 10.1016/j.pneurobio.2016.05.001
    [5]
    YE Y Z, JIN T, ZHANG X, et al. Meisoindigo protects against focal cerebral ischemia-reperfusion injury by inhibiting NLRP3 inflammasome activation and regulating microglia/macrophage polarization via TLR4/NF-κB signaling pathway[J]. Front Cell Neurosci, 2019, 13: 553. doi: 10.3389/fncel.2019.00553
    [6]
    IRING A, TÓTH A, BARANYI M, et al. The dualistic role of the purinergic P2Y12-receptor in an in vivo model of Parkinson's disease: signalling pathway and novel therapeutic targets[J]. Pharmacol Res, 2022, 176: 106045. doi: 10.1016/j.phrs.2021.106045
    [7]
    LIU Y L, WU C F, HOU Z J, et al. Pseudoginsenoside-F11 accelerates microglial phagocytosis of myelin debris and attenuates cerebral ischemic injury through complement receptor 3[J]. Neuroscience, 2020, 426: 33-49. doi: 10.1016/j.neuroscience.2019.11.010
    [8]
    ZANDI S, NAKAO S, CHUN K H, et al. ROCK-isoform-specific polarization of macrophages associated with age-related macular degeneration[J]. Cell Rep, 2015, 10(7): 1173-1186. doi: 10.1016/j.celrep.2015.01.050
    [9]
    VAROL C, MILDNER A, JUNG S. Macrophages: development and tissue specialization[J]. Annu Rev Immunol, 2015, 33: 643-675. doi: 10.1146/annurev-immunol-032414-112220
    [10]
    SAIJO K, GLASS C K. Microglial cell origin and phenotypes in health and disease[J]. Nat Rev Immunol, 2011, 11(11): 775-787. doi: 10.1038/nri3086
    [11]
    WANG J. Preclinical and clinical research on inflammation after intracerebral hemorrhage[J]. Prog Neurobiol, 2010, 92(4): 463-477. doi: 10.1016/j.pneurobio.2010.08.001
    [12]
    GINHOUX F, GRETER M, LEBOEUF M, et al. Fate mapping analysis reveals that adult microglia derive from primitive macrophages[J]. Science, 2010, 330(6005): 841-845. doi: 10.1126/science.1194637
    [13]
    CHIOT A, ZAÏDI S, ILTIS C, et al. Modifying macrophages at the periphery has the capacity to change microglial reactivity and to extend ALS survival[J]. Nat Neurosci, 2020, 23(11): 1339-1351. doi: 10.1038/s41593-020-00718-z
    [14]
    XU Y, CUI K X, LI J, et al. Melatonin attenuates choroidal neovascularization by regulating macrophage/microglia polarization via inhibition of RhoA/ROCK signaling pathway[J]. J Pineal Res, 2020, 69(1): e12660.
    [15]
    庄欣琪, 王玉尊, 王瑶琪, 等. 氢对LPS致BV-2小胶质细胞炎症反应的影响及自噬在其中的作用[J]. 中华麻醉学杂志, 2020, 40(3): 350-354. doi: 10.3760/cma.j.cn131073.20190726.00324
    [16]
    HU X M, LEAK R K, SHI Y J, et al. Microglial and macrophage polarization—new prospects for brain repair[J]. Nat Rev Neurol, 2015, 11(1): 56-64. doi: 10.1038/nrneurol.2014.207
    [17]
    刘太聪, 史永强, 张海鸿. 间充质干细胞在神经病理性疼痛中的作用及机制研究[J]. 实用临床医药杂志, 2022, 26(6): 113-117. doi: 10.7619/jcmp.20213816
    [18]
    ZHANG L J, ZHANG J Q, YOU Z L. Switching of the microglial activation phenotype is a possible treatment for depression disorder[J]. Front Cell Neurosci, 2018, 12: 306.
    [19]
    LARSON-CASEY J L, VAID M, GU L L, et al. Increased flux through the mevalonate pathway mediates fibrotic repair without injury[J]. J Clin Invest, 2019, 129(11): 4962-4978. doi: 10.1172/JCI127959
    [20]
    ALVES A, DIEL L, RAMOS G, et al. Tumor microenvironment and Oral Squamous Cell Carcinoma: a crosstalk between the inflammatory state and tumor cell migration[J]. Oral Oncol, 2021, 112: 105038. doi: 10.1016/j.oraloncology.2020.105038
    [21]
    ZHENG Y, HE R Y, WANG P, et al. Exosomes from LPS-stimulated macrophages induce neuroprotection and functional improvement after ischemic stroke by modulating microglial polarization[J]. Biomater Sci, 2019, 7(5): 2037-2049. doi: 10.1039/C8BM01449C
    [22]
    TANG Y Y, HE Y, ZHANG P, et al. LncRNAs regulate the cytoskeleton and related Rho/ROCK signaling in cancer metastasis[J]. Mol Cancer, 2018, 17(1): 77. doi: 10.1186/s12943-018-0825-x
    [23]
    HEMKEMEYER S A, VOLLMER V, SCHWARZ V, et al. Local Myo9b RhoGAP activity regulates cell motility[J]. J Biol Chem, 2021, 296: 100136. doi: 10.1074/jbc.RA120.013623
    [24]
    GARCÍA-MARISCAL A, LI H, PEDERSEN E, et al. Loss of RhoA promotes skin tumor formation and invasion by upregulation of RhoB[J]. Oncogene, 2018, 37(7): 847-860. doi: 10.1038/onc.2017.333
    [25]
    ALKASALIAS T, ALEXEYENKO A, HENNIG K, et al. RhoA knockout fibroblasts lose tumor-inhibitory capacity in vitro and promote tumor growth in vivo[J]. Proc Natl Acad Sci USA, 2017, 114(8): E1413-E1421.
    [26]
    LAI A Y, MCLAURIN J. Rho-associated protein kinases as therapeutic targets for both vascular and parenchymal pathologies in Alzheimer's disease[J]. J Neurochem, 2018, 144(5): 659-668. doi: 10.1111/jnc.14130
    [27]
    LU W Z, WEN J Y, CHEN Z W. Distinct roles of ROCK1 and ROCK2 on the cerebral ischemia injury and subsequently neurodegenerative changes[J]. Pharmacology, 2020, 105(1/2): 3-8.
    [28]
    SZASZ T, WEBB R C. Rho-mancing to sensitize calcium signaling for contraction in the vasculature: role of rho kinase[J]. Adv Pharmacol, 2017, 78: 303-322.
    [29]
    KANG H, YANG B G, ZHANG K Y, et al. Immunoregulation of macrophages by dynamic ligand presentation via ligand-cation coordination[J]. Nat Commun, 2019, 10(1): 1696. doi: 10.1038/s41467-019-09733-6
    [30]
    KANG H, WONG S H D, PAN Q, et al. Anisotropic ligand nanogeometry modulates the adhesion and polarization state of macrophages[J]. Nano Lett, 2019, 19(3): 1963-1975. doi: 10.1021/acs.nanolett.8b05150
    [31]
    BORRAJO A, RODRIGUEZ-PEREZ A I, VILLAR-CHEDA B, et al. Inhibition of the microglial response is essential for the neuroprotective effects of Rho-kinase inhibitors on MPTP-induced dopaminergic cell death[J]. Neuropharmacology, 2014, 85: 1-8. doi: 10.1016/j.neuropharm.2014.05.021
    [32]
    XUE H, ZHANG Y H, GAO Q S, et al. Sevoflurane post-conditioning ameliorates neuronal deficits and axon demyelination after neonatal hypoxic ischemic brain injury: role of microglia/macrophage[J]. Cell Mol Neurobiol, 2021, 41(8): 1801-1816. doi: 10.1007/s10571-020-00949-5
    [33]
    YU J G, OGAWA K, TOKINAGA Y, et al. Sevoflurane inhibits guanosine 5′-[gamma-thio]triphosphate-stimulated, Rho/Rho-kinase-mediated contraction of isolated rat aortic smooth muscle[J]. Anesthesiology, 2003, 99(3): 646-651. doi: 10.1097/00000542-200309000-00020
    [34]
    ZHANG H F, LI Y H, YU J Z, et al. Rho kinase inhibitor fasudil regulates microglia polarization and function[J]. Neuroimmunomodulation, 2013, 20(6): 313-322. doi: 10.1159/000351221
    [35]
    WEI H X, YAO P S, CHEN P P, et al. Neuronal EphA4 regulates OGD/R-induced apoptosis by promoting alternative activation of microglia[J]. Inflammation, 2019, 42(2): 572-585. doi: 10.1007/s10753-018-0914-4
    [36]
    JING F, ZHANG Y X, LONG T, et al. P2Y12 receptor mediates microglial activation via RhoA/ROCK pathway in the trigeminal nucleus caudalis in a mouse model of chronic migraine[J]. J Neuroinflammation, 2019, 16(1): 217. doi: 10.1186/s12974-019-1603-4
    [37]
    CHEN C, LI Y H, ZHANG Q, et al. Fasudil regulates T cell responses through polarization of BV-2 cells in mice experimental autoimmune encephalomyelitis[J]. Acta Pharmacol Sin, 2014, 35(11): 1428-1438. doi: 10.1038/aps.2014.68
    [38]
    ZHANG X X, YE P, WANG D D, et al. Involvement of RhoA/ROCK signaling in aβ-induced chemotaxis, cytotoxicity and inflammatory response of microglial BV2 cells[J]. Cell Mol Neurobiol, 2019, 39(5): 637-650. doi: 10.1007/s10571-019-00668-6
    [39]
    LU E M, WANG Q, LI S C, et al. Profilin 1 knockdown prevents ischemic brain damage by promoting M2 microglial polarization associated with the RhoA/ROCK pathway[J]. J Neurosci Res, 2020, 98(6): 1198-1212. doi: 10.1002/jnr.24607
    [40]
    REFOLO V, STEFANOVA N. Neuroinflammation and glial phenotypic changes in alpha-synucleinopathies[J]. Front Cell Neurosci, 2019, 13: 263.
    [41]
    SACKMANN V, ANSELL A, SACKMANN C, et al. Anti-inflammatory (M2) macrophage media reduce transmission of oligomeric amyloid beta in differentiated SH-SY5Y cells[J]. Neurobiol Aging, 2017, 60: 173-182. doi: 10.1016/j.neurobiolaging.2017.08.022
    [42]
    张琳, 张伟, 张加强, 等. 利多卡因对大鼠内毒素性肺损伤时Rho/ROCK信号通路的影响[J]. 中华麻醉学杂志, 2019, 39(1): 109-112. doi: 10.3760/cma.j.issn.0254-1416.2019.01.028
    [43]
    SCHEIBLICH H, BICKER G. Regulation of microglial phagocytosis by RhoA/ROCK-inhibiting drugs[J]. Cell Mol Neurobiol, 2017, 37(3): 461-473. doi: 10.1007/s10571-016-0379-7
    [44]
    PENG F, LU L Y, WEI F, et al. The onjisaponin B metabolite tenuifolin ameliorates dopaminergic neurodegeneration in a mouse model of Parkinson′s disease[J]. Neuroreport, 2020, 31(6): 456-465. doi: 10.1097/WNR.0000000000001428
    [45]
    WONG S S C, LEE U M, WANG X M, et al. Role of DLC2 and RhoA/ROCK pathway in formalin induced inflammatory pain in mice[J]. Neurosci Lett, 2019, 709: 134379. doi: 10.1016/j.neulet.2019.134379
    [46]
    LEE J, VILLARREAL O D, CHEN X R, et al. QUAKING regulates microexon alternative splicing of the rho GTPase pathway and controls microglia homeostasis[J]. Cell Rep, 2020, 33(13): 108560. doi: 10.1016/j.celrep.2020.108560
    [47]
    VILLAR-CHEDA B, DOMINGUEZ-MEIJIDE A, JOGLAR B, et al. Involvement of microglial RhoA/Rho-kinase pathway activation in the dopaminergic neuron death. Role of angiotensin via angiotensin type 1 receptors[J]. Neurobiol Dis, 2012, 47(2): 268-279. doi: 10.1016/j.nbd.2012.04.010
    [48]
    HAN X N, LAN X, LI Q, et al. Inhibition of prostaglandin E2 receptor EP3 mitigates thrombin-induced brain injury[J]. J Cereb Blood Flow Metab, 2016, 36(6): 1059-1074. doi: 10.1177/0271678X15606462
    [49]
    ZHU M M, LIN J H, QING P, et al. Manual acupuncture relieves microglia-mediated neuroinflammation in a rat model of traumatic brain injury by inhibiting the RhoA/ROCK2 pathway[J]. Acupunct Med, 2020, 38(6): 426-434. doi: 10.1177/0964528420912248
    [50]
    QIAN Z Y, CHEN H T, XIA M J, et al. Activation of glucagon-like peptide-1 receptor in microglia attenuates neuroinflammation-induced glial scarring via rescuing Arf and Rho GAP adapter protein 3 expressions after nerve injury[J]. Int J Biol Sci, 2022, 18(4): 1328-1346. doi: 10.7150/ijbs.68974
    [51]
    KISHIMA K, TACHIBANA T, YAMANAKA H, et al. Role of Rho-associated coiled-coil containing protein kinase in the spinal cord injury induced neuropathic pain[J]. Spine J, 2021, 21(2): 343-351. doi: 10.1016/j.spinee.2020.08.011
    [52]
    TATSUMI E, YAMANAKA H, KOBAYASHI K, et al. RhoA/ROCK pathway mediates p38 MAPK activation and morphological changes downstream of P2Y12/13 receptors in spinal microglia in neuropathic pain[J]. Glia, 2015, 63(2): 216-228. doi: 10.1002/glia.22745
    [53]
    MUESSEL M J, HARRY G J, ARMSTRONG D L, et al. SDF-1α and LPA modulate microglia potassium channels through rho gtpases to regulate cell morphology[J]. Glia, 2013, 61(10): 1620-1628. doi: 10.1002/glia.22543
    [54]
    MOON M Y, KIM H J, LI Y, et al. Involvement of small GTPase RhoA in the regulation of superoxide production in BV2 cells in response to fibrillar Aβ peptides[J]. Cell Signal, 2013, 25(9): 1861-1869. doi: 10.1016/j.cellsig.2013.05.023
    [55]
    DE CARIS M G, GRIECO M, MAGGI E, et al. Blueberry counteracts BV-2 microglia morphological and functional switch after LPS challenge[J]. Nutrients, 2020, 12(6): 1830. doi: 10.3390/nu12061830
    [56]
    KOCH J C, KUTTLER J, MAASS F, et al. Compassionate use of the ROCK inhibitor fasudil in three patients with amyotrophic lateral sclerosis[J]. Front Neurol, 2020, 11: 173. doi: 10.3389/fneur.2020.00173
  • Related Articles

    [1]CHENG Mei, FANG Zhaohui, CHENG Ruodong, QIAO Lulu. Effect of ultrasonic debridement combined with traditional Chinese medicine foot bath on Wagner grade 2 and 3 ulcer of diabetic foot[J]. Journal of Clinical Medicine in Practice, 2022, 26(17): 116-119. DOI: 10.7619/jcmp.20221212
    [2]CHU Lingling, WANG Jing, YOU Qin, FANG Zhaohui, DOU Lina. Continuous nursing pathway for diabetes foot based on WeChat platform[J]. Journal of Clinical Medicine in Practice, 2021, 25(10): 90-93. DOI: 10.7619/jcmp.20201931
    [3]WANG Yulei, ZHOU Mingwang, JI Xing, SU Yaohui, WEI Changhao, CHEN Wei, FU Zhibin, LI Shenghua. Research progress in the pathogenesis of congenital club foot[J]. Journal of Clinical Medicine in Practice, 2021, 25(8): 109-112. DOI: 10.7619/jcmp.20200626
    [4]YU Xin, MI Zhihua, GAO Ju. Role of autophagy in apoptosis of neurons in brain tissue of rats induced by mechanical ventilation[J]. Journal of Clinical Medicine in Practice, 2019, 23(8): 12-15, 21. DOI: 10.7619/jcmp.201908003
    [5]XUAN Hongmei, XING Liyan, DU Jinyu. Effect of metformin combined with acupoint therapy with low frequency impulse stimulation on repairing neuropathy of patients with diabetic foot[J]. Journal of Clinical Medicine in Practice, 2018, (3): 44-47. DOI: 10.7619/jcmp.201803012
    [6]WANG Yacong, LI Shuli, CHEN Xiaoming. Clinical research of lumbar and epidural anesthesia on analgesia efficacy in puerperae with prolonged incubation delivery[J]. Journal of Clinical Medicine in Practice, 2017, (15): 92-94. DOI: 10.7619/jcmp.201715025
    [7]DOU Shoukun. Effect of health education pathway on rehabilitation of children with hand foot and mouth disease[J]. Journal of Clinical Medicine in Practice, 2016, (14): 134-136,143. DOI: 10.7619/jcmp.201614042
    [8]LIU Jialu, WEI Lihong, YANG Yinhua, XU Xiaoming. The effect of clinical nursing pathway in patients with hand-foot-mouth disease[J]. Journal of Clinical Medicine in Practice, 2015, (22): 103-104,107. DOI: 10.7619/jcmp.201522034
    [9]QIU Haimin, QIAO Genfang. Evaluation of nursing intervention for the patients with diabetic foot[J]. Journal of Clinical Medicine in Practice, 2014, (14): 84-86,94. DOI: 10.7619/jcmp.201414027
    [10]QIAO Xiao-ping, Zhang Ying-hui. First aid and nursing care of severe hand- foot- and- mouth disease children with stress gastric ulcer receiving mechanical ventilation[J]. Journal of Clinical Medicine in Practice, 2011, (14): 12-13. DOI: 10.3969/j.issn.1672-2353.2011.14.006
  • Cited by

    Periodical cited type(1)

    1. 喻玲玲. 改良赛丁格尔PICC置管术在乳腺癌化疗患者中的应用. 实用中西医结合临床. 2025(01): 63-66 .

    Other cited types(0)

Catalog

    Article views (404) PDF downloads (33) Cited by(1)

    /

    DownLoad:  Full-Size Img  PowerPoint
    Return
    Return