{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,23]],"date-time":"2026-04-23T20:55:27Z","timestamp":1776977727595,"version":"3.51.4"},"reference-count":42,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2016,6,16]],"date-time":"2016-06-16T00:00:00Z","timestamp":1466035200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2016,6,16]],"date-time":"2016-06-16T00:00:00Z","timestamp":1466035200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Neural\/glial antigen 2 (NG2), a chondroitin sulfate proteoglycan, is significantly upregulated in a subset of glial cells in the facial motor nucleus (FMN) following CNS injury. NG2 is reported to promote the resulting inflammatory reaction, however, the mechanism by which NG2 mediates these effects is yet to be determined. In this study, we examined the changes in NG2 expressing microglial cells in the FMN in response to facial nerve axotomy (FNA) in mice. Our findings indicated that NG2 expression was progressively induced and upregulated specifically in the ipsilateral facial nucleus following FNA. To further investigate the effects of NG2 expression, <jats:italic>in vivo<\/jats:italic> studies in NG2-knockout mice and <jats:italic>in vitro<\/jats:italic> studies in rat microglial cells transfected with NG2 shRNAs were performed. Abolition of NG2 expression both <jats:italic>in vitro<\/jats:italic> and <jats:italic>in vivo<\/jats:italic> resulted in increased expression of neurotrophic factors (nerve growth factor and glial derived neurotrophic factor), decreased expression of inflammatory mediators (tumor necrosis factor-\u03b1 and interleukin-1\u03b2) and decreased apoptosis in the ipsilateral facial nucleus in response to FNA. Furthermore, we demonstrated the role of FAK in these NG2-induced effects. Taken together, our findings suggest that NG2 expression mediates inflammatory reactions and neurodegeneration in microglial cells in response to CNS injury, potentially by regulating FAK phosphorylation.<\/jats:p>","DOI":"10.1038\/srep27983","type":"journal-article","created":{"date-parts":[[2016,6,16]],"date-time":"2016-06-16T09:58:47Z","timestamp":1466071127000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["NG2 expression in microglial cells affects the expression of neurotrophic and proinflammatory factors by regulating FAK phosphorylation"],"prefix":"10.1038","volume":"6","author":[{"given":"Lie","family":"Zhu","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qing","family":"Su","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiang","family":"Jie","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Antang","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hui","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Beiping","family":"He","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hua","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2016,6,16]]},"reference":[{"key":"BFsrep27983_CR1","doi-asserted-by":"publisher","first-page":"469","DOI":"10.1023\/A:1025739630398","volume":"31","author":"PJ Horner","year":"2002","unstructured":"Horner, P. J., Thallmair, M. & Gage, F. H. Defining the NG2-expressing cell of the adult CNS. J Neurocytol 31, 469\u2013480 (2002).","journal-title":"J Neurocytol"},{"key":"BFsrep27983_CR2","doi-asserted-by":"publisher","first-page":"345","DOI":"10.1023\/B:NEUR.0000044195.64009.27","volume":"33","author":"A Peters","year":"2004","unstructured":"Peters, A. A fourth type of neuroglial cell in the adult central nervous system. J Neurocytol 33, 345\u2013357 (2004).","journal-title":"J Neurocytol"},{"key":"BFsrep27983_CR3","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1038\/nrn2495","volume":"10","author":"A Nishiyama","year":"2009","unstructured":"Nishiyama, A., Komitova, M., Suzuki, R. & Zhu, X. Polydendrocytes (NG2 cells): multifunctional cells with lineage plasticity. Nat Rev Neurosci 10, 9\u201322 (2009).","journal-title":"Nat Rev Neurosci"},{"key":"BFsrep27983_CR4","first-page":"245","volume":"3","author":"JM Levine","year":"1996","unstructured":"Levine, J. M. & Nishiyama, A. The NG2 chondroitin sulfate proteoglycan: a multifunctional proteoglycan associated with immature cells. Perspect Dev Neurobiol 3, 245\u2013259 (1996).","journal-title":"Perspect Dev Neurobiol"},{"key":"BFsrep27983_CR5","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1016\/S0166-2236(00)01691-X","volume":"24","author":"JM Levine","year":"2001","unstructured":"Levine, J. M., Reynolds, R. & Fawcett, J. W. The oligodendrocyte precursor cell in health and disease. Trends Neurosci 24, 39\u201347 (2001).","journal-title":"Trends Neurosci"},{"key":"BFsrep27983_CR6","doi-asserted-by":"publisher","first-page":"18","DOI":"10.1186\/1750-1326-3-18","volume":"3","author":"YJ Wu","year":"2008","unstructured":"Wu, Y. J., Tang, Y. F., Xiao, Z. C., Bao, Z. M. & He, B. P. NG2 cells response to axonal alteration in the spinal cord white matter in mice with genetic disruption of neurofilament light subunit expression. Mol Neurodegener 3, 18 (2008).","journal-title":"Mol Neurodegener"},{"key":"BFsrep27983_CR7","doi-asserted-by":"publisher","first-page":"144","DOI":"10.1179\/174313209X393555","volume":"31","author":"A Wang","year":"2009","unstructured":"Wang, A. & He, B. P. Characteristics and functions of NG2 cells in normal brain and neuropathology. Neurol Res 31, 144\u2013150 (2009).","journal-title":"Neurol Res"},{"key":"BFsrep27983_CR8","doi-asserted-by":"publisher","first-page":"77","DOI":"10.1016\/S0165-0173(99)00007-7","volume":"30","author":"G Raivich","year":"1999","unstructured":"Raivich, G. et al. Neuroglial activation repertoire in the injured brain: graded response, molecular mechanisms and cues to physiological function. Brain Res Brain Res Rev 30, 77\u2013105 (1999).","journal-title":"Brain Res Brain Res Rev"},{"key":"BFsrep27983_CR9","doi-asserted-by":"publisher","first-page":"563","DOI":"10.1016\/S0301-0082(98)00069-0","volume":"57","author":"WJ Streit","year":"1999","unstructured":"Streit, W. J., Walter, S. A. & Pennell, N. A. Reactive microgliosis. Prog Neurobiol 57, 563\u2013581 (1999).","journal-title":"Prog Neurobiol"},{"key":"BFsrep27983_CR10","doi-asserted-by":"publisher","first-page":"121","DOI":"10.1002\/(SICI)1098-1136(199606)17:2<121::AID-GLIA4>3.0.CO;2-5","volume":"17","author":"JC Moller","year":"1996","unstructured":"Moller, J. C. et al. Regulation of thrombospondin in the regenerating mouse facial motor nucleus. Glia 17, 121\u2013132 (1996).","journal-title":"Glia"},{"key":"BFsrep27983_CR11","doi-asserted-by":"publisher","first-page":"248","DOI":"10.1002\/cne.902680209","volume":"268","author":"WJ Streit","year":"1988","unstructured":"Streit, W. J. & Kreutzberg, G. W. Response of endogenous glial cells to motor neuron degeneration induced by toxic ricin. J Comp Neurol 268, 248\u2013263 (1988).","journal-title":"J Comp Neurol"},{"key":"BFsrep27983_CR12","doi-asserted-by":"publisher","first-page":"379","DOI":"10.1007\/s004410050944","volume":"290","author":"MT Fitch","year":"1997","unstructured":"Fitch, M. T. & Silver, J. Glial cell extracellular matrix: boundaries for axon growth in development and regeneration. Cell Tissue Res 290, 379\u2013384 (1997).","journal-title":"Cell Tissue Res"},{"key":"BFsrep27983_CR13","doi-asserted-by":"publisher","first-page":"51","DOI":"10.1006\/exnr.1999.7184","volume":"160","author":"ML Lemons","year":"1999","unstructured":"Lemons, M. L., Howland, D. R. & Anderson, D. K. Chondroitin sulfate proteoglycan immunoreactivity increases following spinal cord injury and transplantation. Exp Neurol 160, 51\u201365 (1999).","journal-title":"Exp Neurol"},{"key":"BFsrep27983_CR14","doi-asserted-by":"publisher","first-page":"842","DOI":"10.1016\/j.neuroscience.2009.12.057","volume":"166","author":"L Zhu","year":"2010","unstructured":"Zhu, L., Lu, J., Tay, S. S., Jiang, H. & He, B. P. Induced NG2 expressing microglia in the facial motor nucleus after facial nerve axotomy. Neuroscience 166, 842\u2013851 (2010).","journal-title":"Neuroscience"},{"key":"BFsrep27983_CR15","doi-asserted-by":"publisher","first-page":"386","DOI":"10.1016\/j.neuroscience.2009.10.022","volume":"165","author":"Q Gao","year":"2010","unstructured":"Gao, Q. et al. NG2, a member of chondroitin sulfate proteoglycans family mediates the inflammatory response of activated microglia. Neuroscience 165, 386\u2013394 (2010).","journal-title":"Neuroscience"},{"key":"BFsrep27983_CR16","doi-asserted-by":"publisher","first-page":"111","DOI":"10.1002\/glia.440070117","volume":"7","author":"RB Banati","year":"1993","unstructured":"Banati, R. B., Gehrmann, J., Schubert, P. & Kreutzberg, G. W. Cytotoxicity of microglia. Glia 7, 111\u2013118 (1993).","journal-title":"Glia"},{"key":"BFsrep27983_CR17","doi-asserted-by":"publisher","first-page":"1200","DOI":"10.1111\/j.1471-4159.2006.03964.x","volume":"98","author":"C Kaur","year":"2006","unstructured":"Kaur, C., Sivakumar, V., Ang, L. S. & Sundaresan, A. Hypoxic damage to the periventricular white matter in neonatal brain: role of vascular endothelial growth factor, nitric oxide and excitotoxicity. J Neurochem 98, 1200\u20131216 (2006).","journal-title":"J Neurochem"},{"issue":"3","key":"BFsrep27983_CR18","doi-asserted-by":"publisher","first-page":"603","DOI":"10.1038\/jcbfm.2009.233","volume":"30","author":"Anna Smirkin","year":"2009","unstructured":"Smirkin, A. et al. Iba1(+)\/NG2(+) macrophage-like cells expressing a variety of neuroprotective factors ameliorate ischemic damage of the brain. J Cereb Blood Flow Metab 30, (2010).","journal-title":"Journal of Cerebral Blood Flow & Metabolism"},{"key":"BFsrep27983_CR19","doi-asserted-by":"publisher","first-page":"1417","DOI":"10.1002\/glia.22362","volume":"60","author":"L Zhu","year":"2012","unstructured":"Zhu, L. et al. Microglia\/monocytes with NG2 expression have no phagocytic function in the cortex after LPS focal injection into the rat brain. Glia 60, 1417\u20131426 (2012).","journal-title":"Glia"},{"key":"BFsrep27983_CR20","doi-asserted-by":"publisher","first-page":"463","DOI":"10.1146\/annurev.cellbio.12.1.463","volume":"12","author":"K Burridge","year":"1996","unstructured":"Burridge, K. & Chrzanowska-Wodnicka, M. Focal adhesions, contractility and signaling. Annu Rev Cell Dev Biol 12, 463\u2013518 (1996).","journal-title":"Annu Rev Cell Dev Biol"},{"key":"BFsrep27983_CR21","doi-asserted-by":"publisher","first-page":"435","DOI":"10.1016\/S0079-6107(98)00052-2","volume":"71","author":"DD Schlaepfer","year":"1999","unstructured":"Schlaepfer, D. D., Hauck, C. R. & Sieg, D. J. Signaling through focal adhesion kinase. Prog Biophys Mol Biol 71, 435\u2013478 (1999).","journal-title":"Prog Biophys Mol Biol"},{"key":"BFsrep27983_CR22","doi-asserted-by":"publisher","first-page":"505","DOI":"10.1038\/nrc1647","volume":"5","author":"GW McLean","year":"2005","unstructured":"McLean, G. W. et al. The role of focal-adhesion kinase in cancer-a new therapeutic opportunity. Nat Rev Cancer 5, 505\u2013515 (2005).","journal-title":"Nat Rev Cancer"},{"key":"BFsrep27983_CR23","doi-asserted-by":"publisher","first-page":"881","DOI":"10.1083\/jcb.200403174","volume":"165","author":"J Yang","year":"2004","unstructured":"Yang, J. et al. Melanoma chondroitin sulfate proteoglycan enhances FAK and ERK activation by distinct mechanisms. J Cell Biol 165, 881\u2013891 (2004).","journal-title":"J Cell Biol"},{"key":"BFsrep27983_CR24","doi-asserted-by":"crossref","unstructured":"Xiang, P., Zhu, L., Jiang, H. & He, B. P. The activation of NG2 expressing cells is downstream to microglial reaction and mediated by the transforming growth factor beta 1. J Neuroimmunol 279, (2015).","DOI":"10.1016\/j.jneuroim.2015.01.006"},{"key":"BFsrep27983_CR25","doi-asserted-by":"publisher","first-page":"471","DOI":"10.1002\/1097-4547(20000901)61:5<471::AID-JNR1>3.0.CO;2-N","volume":"61","author":"MR Dawson","year":"2000","unstructured":"Dawson, M. R., Levine, J. M. & Reynolds, R. NG2-expressing cells in the central nervous system: are they oligodendroglial progenitors? J Neurosci Res 61, 471\u2013479 (2000).","journal-title":"J Neurosci Res"},{"key":"BFsrep27983_CR26","doi-asserted-by":"publisher","first-page":"754","DOI":"10.1002\/glia.20332","volume":"53","author":"A Yokoyama","year":"2006","unstructured":"Yokoyama, A., Sakamoto, A., Kameda, K., Imai, Y. & Tanaka, J. NG2 proteoglycan-expressing microglia as multipotent neural progenitors in normal and pathologic brains. Glia 53, 754\u2013768 (2006).","journal-title":"Glia"},{"key":"BFsrep27983_CR27","doi-asserted-by":"publisher","first-page":"491","DOI":"10.1097\/00004647-199705000-00002","volume":"17","author":"H Uno","year":"1997","unstructured":"Uno, H., Matsuyama, T., Akita, H., Nishimura, H. & Sugita, M. Induction of tumor necrosis factor-alpha in the mouse hippocampus following transient forebrain ischemia. J Cereb Blood Flow Metab 17, 491\u2013499 (1997).","journal-title":"J Cereb Blood Flow Metab"},{"key":"BFsrep27983_CR28","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1002\/glia.20153","volume":"50","author":"ST Dheen","year":"2005","unstructured":"Dheen, S. T., Jun, Y., Yan, Z., Tay, S. S. & Ling, E. A. Retinoic acid inhibits expression of TNF-alpha and iNOS in activated rat microglia. Glia 50, 21\u201331 (2005).","journal-title":"Glia"},{"key":"BFsrep27983_CR29","doi-asserted-by":"publisher","first-page":"1179","DOI":"10.1523\/JNEUROSCI.21-04-01179.2001","volume":"21","author":"CK Combs","year":"2001","unstructured":"Combs, C. K., Karlo, J. C., Kao, S. C. & Landreth, G. E. beta-Amyloid stimulation of microglia and monocytes results in TNFalpha-dependent expression of inducible nitric oxide synthase and neuronal apoptosis. J Neurosci 21, 1179\u20131188 (2001).","journal-title":"J Neurosci"},{"key":"BFsrep27983_CR30","first-page":"2496","volume":"42","author":"L You","year":"2001","unstructured":"You, L., Ebner, S. & Kruse, F. E. Glial cell-derived neurotrophic factor (GDNF)-induced migration and signal transduction in corneal epithelial cells. Invest Ophthalmol Vis Sci 42, 2496\u20132504 (2001).","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"BFsrep27983_CR31","doi-asserted-by":"publisher","first-page":"E97","DOI":"10.1038\/ncb0402-e97","volume":"4","author":"DJ Webb","year":"2002","unstructured":"Webb, D. J., Parsons, J. T. & Horwitz, A. F. Adhesion assembly, disassembly and turnover in migrating cells\u2013over and over and over again. Nat Cell Biol 4, E97\u2013100 (2002).","journal-title":"Nat Cell Biol"},{"key":"BFsrep27983_CR32","doi-asserted-by":"publisher","first-page":"249","DOI":"10.1111\/eos.12191","volume":"123","author":"P Zhang","year":"2015","unstructured":"Zhang, P. et al. Focal adhesion kinase activation is required for TNF-alpha-induced production of matrix metalloproteinase-2 and proinflammatory cytokines in cultured human periodontal ligament fibroblasts. Eur J Oral Sci 123, 249\u2013253 (2015).","journal-title":"Eur J Oral Sci"},{"key":"BFsrep27983_CR33","doi-asserted-by":"publisher","first-page":"793","DOI":"10.1083\/jcb.134.3.793","volume":"134","author":"SM Frisch","year":"1996","unstructured":"Frisch, S. M., Vuori, K., Ruoslahti, E. & Chan-Hui, P. Y. Control of adhesion-dependent cell survival by focal adhesion kinase. J Cell Biol 134, 793\u2013799 (1996).","journal-title":"J Cell Biol"},{"key":"BFsrep27983_CR34","doi-asserted-by":"publisher","first-page":"547","DOI":"10.1083\/jcb.143.2.547","volume":"143","author":"D Ilic","year":"1998","unstructured":"Ilic, D. et al. Extracellular matrix survival signals transduced by focal adhesion kinase suppress p53-mediated apoptosis. J Cell Biol 143, 547\u2013560 (1998).","journal-title":"J Cell Biol"},{"key":"BFsrep27983_CR35","doi-asserted-by":"publisher","first-page":"185","DOI":"10.1016\/j.neuroscience.2009.12.014","volume":"166","author":"K Kucharova","year":"2010","unstructured":"Kucharova, K. & Stallcup, W. B. The NG2 proteoglycan promotes oligodendrocyte progenitor proliferation and developmental myelination. Neuroscience 166, 185\u2013194 (2010).","journal-title":"Neuroscience"},{"key":"BFsrep27983_CR36","doi-asserted-by":"publisher","first-page":"2163","DOI":"10.1523\/JNEUROSCI.06-08-02163.1986","volume":"6","author":"D Giulian","year":"1986","unstructured":"Giulian, D. & Baker, T. J. Characterization of ameboid microglia isolated from developing mammalian brain. J Neurosci 6, 2163\u20132178 (1986).","journal-title":"J Neurosci"},{"key":"BFsrep27983_CR37","doi-asserted-by":"publisher","first-page":"183","DOI":"10.1002\/glia.10274","volume":"44","author":"J Saura","year":"2003","unstructured":"Saura, J., Tusell, J. M. & Serratosa, J. High-yield isolation of murine microglia by mild trypsinization. Glia 44, 183\u2013189 (2003).","journal-title":"Glia"},{"key":"BFsrep27983_CR38","doi-asserted-by":"publisher","first-page":"863","DOI":"10.1002\/jgm.1509","volume":"12","author":"EM Donnelly","year":"2010","unstructured":"Donnelly, E. M. et al. Lentiviral vector-mediated knockdown of the NG2 [corrected] proteoglycan or expression of neurotrophin-3 promotes neurite outgrowth in a cell culture model of the glial scar. J Gene Med 12, 863\u2013872 (2010).","journal-title":"J Gene Med"},{"key":"BFsrep27983_CR39","doi-asserted-by":"publisher","first-page":"248","DOI":"10.1016\/0003-2697(76)90527-3","volume":"72","author":"MM Bradford","year":"1976","unstructured":"Bradford, M. M. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 72, 248\u2013254 (1976).","journal-title":"Anal Biochem"},{"key":"BFsrep27983_CR40","doi-asserted-by":"publisher","first-page":"22","DOI":"10.1016\/j.autneu.2008.04.007","volume":"141","author":"C Gao","year":"2008","unstructured":"Gao, C. et al. Anti-apoptotic and neuroprotective effects of Tetramethylpyrazine following subarachnoid hemorrhage in rats. Auton Neurosci 141, 22\u201330 (2008).","journal-title":"Auton Neurosci"},{"key":"BFsrep27983_CR41","doi-asserted-by":"publisher","first-page":"402","DOI":"10.1006\/meth.2001.1262","volume":"25","author":"KJ Livak","year":"2001","unstructured":"Livak, K. J. & Schmittgen, T. D. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods 25, 402\u2013408 (2001).","journal-title":"Methods"},{"key":"BFsrep27983_CR42","doi-asserted-by":"publisher","first-page":"2417","DOI":"10.1016\/j.fct.2012.04.041","volume":"50","author":"H Sang","year":"2012","unstructured":"Sang, H., Zhang, L. & Li, J. Anti-benzopyrene-7,8-diol-9,10-epoxide induces apoptosis via mitochondrial pathway in human bronchiolar epithelium cells independent of the mitochondria permeability transition pore. Food and chemical toxicology: an international journal published for the British Industrial Biological Research Association 50, 2417\u20132423 (2012).","journal-title":"Food and chemical toxicology: an international journal published for the British Industrial Biological Research Association"}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/srep27983","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/srep27983.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/srep27983.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,1,4]],"date-time":"2023-01-04T17:31:22Z","timestamp":1672853482000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/srep27983"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,6,16]]},"references-count":42,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2016,9,13]]}},"alternative-id":["BFsrep27983"],"URL":"https:\/\/doi.org\/10.1038\/srep27983","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,6,16]]},"assertion":[{"value":"1 February 2016","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"27 May 2016","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"16 June 2016","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing financial interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"27983"}}