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Cited by 25Neuroinflammation and Neurodegeneration MechanismsWnt/β-catenin signaling in development and cancerNeuroscience and Neuropharmacology Research

β-Catenin Regulates Wound Healing and IL-6 Expression in Activated Human Astrocytes

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Edara, Venkata Viswanadh, Nooka, Shruthi, Proulx, Jessica, Stacy, Satomi, Ghorpade, Anuja, Borgmann, Kathleen·2020·Biomedicines
DOI 10.3390/biomedicines8110479PMC PMC7694627
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Abstract

Reactive astrogliosis is prominent in most neurodegenerative disorders and is often associated with neuroinflammation. The molecular mechanisms regulating astrocyte-linked neuropathogenesis during injury, aging and human immunodeficiency virus (HIV)-associated neurocognitive disorders (HAND) are not fully understood. In this study, we investigated the implications of the wingless type (Wnt)/β-catenin signaling pathway in regulating astrocyte function during gliosis. First, we identified that HIV-associated inflammatory cytokines, interleukin (IL)-1β and tumor necrosis factor (TNF)-α induced mediators of the Wnt/β-catenin pathway including β-catenin and lymphoid enhancer-binding factor (LEF)-1 expression in astrocytes. Next, we investigated the regulatory role of β-catenin on primary aspects of reactive astrogliosis, including proliferation, migration and proinflammatory responses, such as IL-6. Knockdown of β-catenin impaired astrocyte proliferation and migration as shown by reduced cyclin-D1 levels, bromodeoxyuridine incorporation and wound healing. HIV-associated cytokines, IL-1β alone and in combination with TNF-α, strongly induced the expression of proinflammatory cytokines including C-C motif chemokine ligand (CCL)2, C-X-C motif chemokine ligand (CXCL)8 and IL-6; however, only IL-6 levels were regulated by β-catenin as demonstrated by knockdown and pharmacological stabilization. In this context, IL-6 levels were negatively regulated by β-catenin. To better understand this relationship, we examined the crossroads between β-catenin and nuclear factor (NF)-κB pathways. While NF-κB expression was significantly increased by IL-1β and TNF-α, NF-κB levels were not affected by β-catenin knockdown. IL-1β treatment significantly increased glycogen synthase kinase (GSK)-3β phosphorylation, which inhibits β-catenin degradation. Further, pharmacological inhibition of GSK-3β increased nuclear translocation of both β-catenin and NF-κB p65 into the nucleus in the absence of any other inflammatory stimuli. HIV+ human astrocytes show increased IL-6, β-catenin and NF-κB expression levels and are interconnected by regulatory associations during HAND. In summary, our study demonstrates that HIV-associated inflammation increases β-catenin pathway mediators to augment activated astrocyte responses including migration and proliferation, while mitigating IL-6 expression. These findings suggest that β-catenin plays an anti-inflammatory role in activated human astrocytes during neuroinflammatory pathologies, such as HAND.

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  1. [2]Heaton R.K. Franklin D.R. Ellis R.J. McCutchan J.A. Letendre S.L. Leblanc S. Corkran S.H. Duarte N.A. Clifford D.B. Woods S.P. HIV-associated neurocognitive disorders before and during the era of combination antiretroviral therapy: Differences in rates, nature, and predictors J. Neurovirol. 2011 17 3 16 10.1007/s13365-010-0006-1 21174240 PMC3032197 · DOI
  2. [3]Spudich S. Gonzalez-Scarano F. HIV-1-related central nervous system disease: Current issues in pathogenesis, diagnosis, and treatment Cold Spring Harb. Perspect. Med. 2012 2 a007120 10.1101/cshperspect.a007120 22675662 PMC3367536 · DOI
  3. [4]Louboutin J.P. Strayer D. Role of Oxidative Stress in HIV-1-Associated Neurocognitive Disorder and Protection by Gene Delivery of Antioxidant Enzymes Antioxidants 2014 3 770 797 10.3390/antiox3040770 26785240 PMC4665507 · DOI
  4. [5]Alvarez J.I. Katayama T. Prat A. Glial influence on the blood brain barrier Glia 2013 61 1939 1958 10.1002/glia.22575 24123158 PMC4068281 · DOI
  5. [6]Lundgaard I. Osorio M.J. Kress B.T. Sanggaard S. Nedergaard M. White matter astrocytes in health and disease Neuroscience 2014 276 161 173 10.1016/j.neuroscience.2013.10.050 24231735 PMC4016995 · DOI
  6. [7]Sofroniew M.V. Vinters H.V. Astrocytes: Biology and pathology Acta Neuropathol. 2010 119 7 35 10.1007/s00401-009-0619-8 20012068 PMC2799634 · DOI · Paper page
  7. [8]Li K. Li J. Zheng J. Qin S. Reactive Astrocytes in Neurodegenerative Diseases Aging Dis. 2019 10 664 675 10.14336/AD.2018.0720 31165009 PMC6538217 · DOI · Paper page
  8. [9]Colangelo A.M. Alberghina L. Papa M. Astrogliosis as a therapeutic target for neurodegenerative diseases Neurosci. Lett. 2014 565 59 64 10.1016/j.neulet.2014.01.014 24457173 · DOI
  9. [10]Brabers N.A. Nottet H.S. Role of the pro-inflammatory cytokines TNF-alpha and IL-1beta in HIV-associated dementia Eur. J. Clin. Investig. 2006 36 447 458 10.1111/j.1365-2362.2006.01657.x 16796601 · DOI
  10. [11]Kaul M. Garden G.A. Lipton S.A. Pathways to neuronal injury and apoptosis in HIV-1-associated dementia Nature 2001 410 988 993 10.1038/35073667 11309629 · DOI
  11. [12]Sharief M.K. Ciardi M. Thompson E.J. Sorice F. Rossi F. Vullo V. Cirelli A. Tumour necrosis factor-alpha mediates blood-brain barrier damage in HIV-1 infection of the central nervous system Mediat. Inflamm. 1992 1 191 196 10.1155/S0962935192000292 PMC2365337 18475460 · DOI
  12. [13]Perrella O. Guerriero M. Izzo E. Soscia M. Carrieri P.B. Interleukin-6 and granulocyte macrophage-CSF in the cerebrospinal fluid from HIV infected subjects with involvement of the central nervous system Arq. Neuropsiquiatr. 1992 50 180 182 10.1590/S0004-282X1992000200008 1308387 · DOI
  13. [14]Achim C.L. Heyes M.P. Wiley C.A. Quantitation of human immunodeficiency virus, immune activation factors, and quinolinic acid in AIDS brains J. Clin. Investig. 1993 91 2769 2775 10.1172/JCI116518 8514884 PMC443343 · DOI
  14. [15]Choi S.S. Lee H.J. Lim I. Satoh J. Kim S.U. Human astrocytes: Secretome profiles of cytokines and chemokines PLoS ONE 2014 9 e92325 10.1371/journal.pone.0092325 24691121 PMC3972155 · DOI
  15. [16]Fields J. Ghorpade A. C/EBPbeta regulates multiple IL-1beta-induced human astrocyte inflammatory genes J. Neuroinflamm. 2012 9 177 10.1186/1742-2094-9-177 PMC3464795 22818222 · DOI
  16. [17]Suryadevara R. Holter S. Borgmann K. Persidsky R. Labenz-Zink C. Persidsky Y. Gendelman H.E. Wu L. Ghorpade A. Regulation of tissue inhibitor of metalloproteinase-1 by astrocytes: Links to HIV-1 dementia Glia 2003 44 47 56 10.1002/glia.10266 12951656 PMC3820378 · DOI
  17. [18]Borgmann K. Ghorpade A. HIV-1, methamphetamine and astrocytes at neuroinflammatory Crossroads Front. Microbiol. 2015 6 1143 10.3389/fmicb.2015.01143 26579077 PMC4621459 · DOI
  18. [19]Kaul M. HIV-1 associated dementia: Update on pathological mechanisms and therapeutic approaches Curr. Opin. Neurol. 2009 22 315 320 10.1097/WCO.0b013e328329cf3c 19300249 PMC2779773 · DOI · Paper page
  19. [21]Ghorpade A. Holter S. Borgmann K. Persidsky R. Wu L. HIV-1 and IL-1beta regulate Fas ligand expression in human astrocytes through the NF-kappaB pathway J. Neuroimmunol. 2003 141 141 149 10.1016/S0165-5728(03)00222-4 12965265 · DOI
  20. [22]Li W. Henderson L.J. Major E.O. Al-Harthi L. IFN-gamma mediates enhancement of HIV replication in astrocytes by inducing an antagonist of the beta-catenin pathway (DKK1) in a STAT 3-dependent manner J. Immunol. 2011 186 6771 6778 10.4049/jimmunol.1100099 21562161 PMC3167069 · DOI
  21. [23]Inestrosa N.C. Montecinos-Oliva C. Fuenzalida M. Wnt signaling: Role in Alzheimer disease and schizophrenia J. Neuroimmune Pharmacol. 2012 7 788 807 10.1007/s11481-012-9417-5 23160851 · DOI
  22. [24]Inestrosa N.C. Arenas E. Emerging roles of Wnts in the adult nervous system Nat. Rev. Neurosci. 2010 11 77 86 10.1038/nrn2755 20010950 · DOI
  23. [25]Al-Harthi L. Interplay between Wnt/beta-catenin signaling and HIV: Virologic and biologic consequences in the CNS J. Neuroimmune Pharmacol. 2012 7 731 739 10.1007/s11481-012-9411-y 23065461 PMC3518628 · DOI
  24. [26]Caricasole A. Bakker A. Copani A. Nicoletti F. Gaviraghi G. Terstappen G.C. Two sides of the same coin: Wnt signaling in neurodegeneration and neuro-oncology Biosci. Rep. 2005 25 309 327 10.1007/s10540-005-2893-6 16307379 · DOI
  25. [27]Narasipura S.D. Henderson L.J. Fu S.W. Chen L. Kashanchi F. Al-Harthi L. Role of beta-Catenin and TCF/LEF Family Members in Transcriptional Activity of HIV in Astrocytes J. Virol. 2012 86 1911 1921 10.1128/JVI.06266-11 22156527 PMC3302377 · DOI
  26. [28]Wortman B. Darbinian N. Sawaya B.E. Khalili K. Amini S. Evidence for regulation of long terminal repeat transcription by Wnt transcription factor TCF-4 in human astrocytic cells J. Virol. 2002 76 11159 11165 10.1128/JVI.76.21.11159-11165.2002 12368361 PMC136655 · DOI
  27. [29]Shi Y. Shu J. Gelman B.B. Lisinicchia J.G. Tang S.J. Wnt signaling in the pathogenesis of human HIV-associated pain syndromes J. Neuroimmune Pharmacol. 2013 8 956 964 10.1007/s11481-013-9474-4 23737037 PMC3743252 · DOI
  28. [30]Yuan S.B. Ji G. Li B. Andersson T. Neugebauer V. Tang S.J. A Wnt5a signaling pathway in the pathogenesis of HIV-1 gp120-induced pain Pain 2015 156 1311 1319 10.1097/j.pain.0000000000000177 25840108 PMC4682897 · DOI
  29. [32]Jope R.S. Yuskaitis C.J. Beurel E. Glycogen synthase kinase-3 (GSK3): Inflammation, diseases, and therapeutics Neurochem. Res. 2007 32 577 595 10.1007/s11064-006-9128-5 16944320 PMC1970866 · DOI · Paper page
  30. [33]Maqbool M. Mobashir M. Hoda N. Pivotal role of glycogen synthase kinase-3: A therapeutic target for Alzheimer’s disease Eur. J. Med. Chem. 2016 107 63 81 10.1016/j.ejmech.2015.10.018 26562543 · DOI
  31. [34]Golpich M. Amini E. Hemmati F. Ibrahim N.M. Rahmani B. Mohamed Z. Raymond A.A. Dargahi L. Ghasemi R. Ahmadiani A. Glycogen synthase kinase-3 beta (GSK-3beta) signaling: Implications for Parkinson’s disease Pharmacol. Res. 2015 97 16 26 10.1016/j.phrs.2015.03.010 25829335 · DOI
  32. [35]Gilmore T.D. Introduction to NF-kappaB: Players, pathways, perspectives Oncogene 2006 25 6680 6684 10.1038/sj.onc.1209954 17072321 · DOI
  33. [36]Lawrence T. The nuclear factor NF-kappaB pathway in inflammation Cold Spring Harb. Perspect. Biol. 2009 1 a001651 10.1101/cshperspect.a001651 20457564 PMC2882124 · DOI
  34. [37]Bhakar A.L. Tannis L.L. Zeindler C. Russo M.P. Jobin C. Park D.S. MacPherson S. Barker P.A. Constitutive nuclear factor-kappa B activity is required for central neuron survival J. Neurosci. 2002 22 8466 8475 10.1523/JNEUROSCI.22-19-08466.2002 12351721 PMC6757785 · DOI · Paper page
  35. [38]Schmidt-Ullrich R. Memet S. Lilienbaum A. Feuillard J. Raphael M. Israel A. NF-kappaB activity in transgenic mice: Developmental regulation and tissue specificity Development 1996 122 2117 2128 8681793
  36. [39]Nitkiewicz J. Borjabad A. Morgello S. Murray J. Chao W. Emdad L. Fisher P.B. Potash M.J. Volsky D.J. HIV induces expression of complement component C3 in astrocytes by NF-kappaB-dependent activation of interleukin-6 synthesis J. Neuroinflamm. 2017 14 23 10.1186/s12974-017-0794-9 PMC5267445 28122624 · DOI
  37. [40]Gupta A.S. Waters M.R. Biswas D.D. Brown L.N. Surace M.J. Floros C. Siebenlist U. Kordula T. RelB controls adaptive responses of astrocytes during sterile inflammation Glia 2019 67 1449 1461 10.1002/glia.23619 30957303 PMC6557670 · DOI
  38. [41]Ma B. Hottiger M.O. Crosstalk between Wnt/beta-Catenin and NF-kappaB Signaling Pathway during Inflammation Front. Immunol. 2016 7 378 10.3389/fimmu.2016.00378 27713747 PMC5031610 · DOI
  39. [42]Gardner J. Ghorpade A. Tissue inhibitor of metalloproteinase (TIMP)-1: The TIMPed balance of matrix metalloproteinases in the central nervous system J. Neurosci. Res. 2003 74 801 806 10.1002/jnr.10835 14648584 PMC3857704 · DOI · Paper page
  40. [44]Borgmann K. Gendelman H.E. Ghorpade A. Isolation and HIV-1 infection of primary human microglia from fetal and adult tissue Methods Mol. Biol. 2005 304 49 70 16061966
  41. [45]Liang C.C. Park A.Y. Guan J.L. In vitro scratch assay: A convenient and inexpensive method for analysis of cell migration in vitro Nat. Protoc. 2007 2 329 333 10.1038/nprot.2007.30 17406593 · DOI · Paper page
  42. [46]Manthorpe M. Fagnani R. Skaper S.D. Varon S. An automated colorimetric microassay for neuronotrophic factors Brain Res. 1986 390 191 198 10.1016/0165-3806(86)90208-7 3955369 · DOI
  43. [47]Edara V.V. Ghorpade A. Borgmann K. Insights into the Gene Expression Profiles of Active and Restricted Red/Green-HIV(+) Human Astrocytes: Implications for Shock or Lock Therapies in the Brain J. Virol. 2020 94 10.1128/JVI.01563-19 PMC7158706 31896591 · DOI
  44. [48]Shtutman M. Zhurinsky J. Simcha I. Albanese C. D’Amico M. Pestell R. Ben-Ze’ev A. The cyclin D1 gene is a target of the beta-catenin/LEF-1 pathway Proc. Natl. Acad. Sci. USA 1999 96 5522 5527 10.1073/pnas.96.10.5522 10318916 PMC21892 · DOI · Paper page
  45. [49]Sofroniew M.V. Molecular dissection of reactive astrogliosis and glial scar formation Trends Neurosci. 2009 32 638 647 10.1016/j.tins.2009.08.002 19782411 PMC2787735 · DOI · Paper page
  46. [50]Sofroniew M.V. Reactive astrocytes in neural repair and protection Neurosci. Rev. J. Bringing Neurobiol. Neurol. Psychiatry 2005 11 400 407 10.1177/1073858405278321 16151042 · DOI
  47. [51]Kafri P. Hasenson S.E. Kanter I. Sheinberger J. Kinor N. Yunger S. Shav-Tal Y. Quantifying beta-catenin subcellular dynamics and cyclin D1 mRNA transcription during Wnt signaling in single living cells Elife 2016 5 10.7554/eLife.16748 PMC5161448 27879202 · DOI
  48. [52]Lutgen V. Narasipura S.D. Barbian H.J. Richards M. Wallace J. Razmpour R. Buzhdygan T. Ramirez S.H. Prevedel L. Eugenin E.A. HIV infects astrocytes in vivo and egresses from the brain to the periphery PLoS Pathog. 2020 16 e1008381 10.1371/journal.ppat.1008381 32525948 PMC7289344 · DOI
  49. [53]Han Y. He T. Huang D.R. Pardo C.A. Ransohoff R.M. TNF-alpha mediates SDF-1 alpha-induced NF-kappa B activation and cytotoxic effects in primary astrocytes J. Clin. Investig. 2001 108 425 435 10.1172/JCI12629 11489936 PMC209361 · DOI
  50. [54]Zhao M. Kim M. Morgello S. Lee S.C. Expression of inducible nitric oxide synthase, interleukin-1 and caspase-1 in HIV-1 encephalitis J. Neuroimmunol. 2001 115 182 191 10.1016/S0165-5728(00)00463-X 11282169 · DOI
  51. [55]Dragon S. Rahman M.S. Yang J. Unruh H. Halayko A.J. Gounni A.S. IL-17 enhances IL-1beta-mediated CXCL-8 release from human airway smooth muscle cells Am. J. Physiol. Lung Cell Mol. Physiol. 2007 292 L1023 L1029 10.1152/ajplung.00306.2006 17189320 · DOI
  52. [56]Hu W. Li F. Mahavadi S. Murthy K.S. Upregulation of RGS4 expression by IL-1beta in colonic smooth muscle is enhanced by ERK1/2 and p38 MAPK and inhibited by the PI3K/Akt/GSK3beta pathway Am. J. Physiol. Cell Physiol. 2009 296 C1310 C1320 10.1152/ajpcell.00573.2008 19369446 PMC2692422 · DOI
  53. [57]Nejak-Bowen K. Kikuchi A. Monga S.P. Beta-catenin-NF-kappaB interactions in murine hepatocytes: A complex to die for Hepatology 2013 57 763 774 10.1002/hep.26042 22941935 PMC3566301 · DOI
  54. [58]Jang J. Ha J.H. Chung S.I. Yoon Y. Beta-catenin regulates NF-kappaB activity and inflammatory cytokine expression in bronchial epithelial cells treated with lipopolysaccharide Int. J. Mol. Med. 2014 34 632 638 10.3892/ijmm.2014.1807 24938929 · DOI
  55. [59]Schon S. Flierman I. Ofner A. Stahringer A. Holdt L.M. Kolligs F.T. Herbst A. beta-catenin regulates NF-kappaB activity via TNFRSF19 in colorectal cancer cells Int. J. Cancer 2014 135 1800 1811 10.1002/ijc.28839 24623448 · DOI
  56. [60]Vines A. Cahoon S. Goldberg I. Saxena U. Pillarisetti S. Novel anti-inflammatory role for glycogen synthase kinase-3beta in the inhibition of tumor necrosis factor-alpha- and interleukin-1beta-induced inflammatory gene expression J. Biol. Chem. 2006 281 16985 16990 10.1074/jbc.M602446200 16601113 · DOI
  57. [61]Robinson K.F. Narasipura S.D. Wallace J. Ritz E.M. Al-Harthi L. β-Catenin and TCFs/LEF signaling discordantly regulate IL-6 expression in astrocytes Cell Commun. Signal. 2020 18 93 10.1186/s12964-020-00565-2 32546183 PMC7296971 · DOI
  58. [62]Norris J.G. Tang L.P. Sparacio S.M. Benveniste E.N. Signal transduction pathways mediating astrocyte IL-6 induction by IL-1 beta and tumor necrosis factor-alpha J. Immunol. 1994 152 841 850 7506738
  59. [63]Hunt P.W. Sinclair E. Rodriguez B. Shive C. Clagett B. Funderburg N. Robinson J. Huang Y. Epling L. Martin J.N. Gut epithelial barrier dysfunction and innate immune activation predict mortality in treated HIV infection J. Infect. Dis. 2014 210 1228 1238 10.1093/infdis/jiu238 24755434 PMC4192038 · DOI
  60. [65]Tenorio A.R. Zheng Y. Bosch R.J. Krishnan S. Rodriguez B. Hunt P.W. Plants J. Seth A. Wilson C.C. Deeks S.G. Soluble markers of inflammation and coagulation but not T-cell activation predict non-AIDS-defining morbid events during suppressive antiretroviral treatment J. Infect. Dis. 2014 210 1248 1259 10.1093/infdis/jiu254 24795473 PMC4192039 · DOI
  61. [66]Poli G. Bressler P. Kinter A. Duh E. Timmer W. Rabson A. Justement S. Stanley S. Fauci A. Interleukin 6 induces human immunodeficiency virus expression in infected monocytic cells alone and in synergy with tumor necrosis factor-alpha by transcriptional and post-transcriptional mechanisms J. Exp. Med. 1990 172 151 158 10.1084/jem.172.1.151 2193094 PMC2188185 · DOI
  62. [67]Poli G. Fauci A.S. The effect of cytokines and pharmacologic agents on chronic HIV infection AIDS Res. Hum. Retrovir. 1992 8 191 197 10.1089/aid.1992.8.191 1540407 · DOI
  63. [68]Lynch H.E. Goldberg G.L. Chidgey A. Van den Brink M.R. Boyd R. Sempowski G.D. Thymic involution and immune reconstitution Trends Immunol. 2009 30 366 373 10.1016/j.it.2009.04.003 19540807 PMC2750859 · DOI · Paper page
  64. [69]Airoldi M. Bandera A. Trabattoni D. Tagliabue B. Arosio B. Soria A. Rainone V. Lapadula G. Annoni G. Clerici M. Neurocognitive impairment in HIV-infected naive patients with advanced disease: The role of virus and intrathecal immune activation Clin. Dev. Immunol. 2012 2012 467154 10.1155/2012/467154 22489249 PMC3320013 · DOI
  65. [70]Velazquez-Salinas L. Verdugo-Rodriguez A. Rodriguez L.L. Borca M.V. The Role of Interleukin 6 During Viral Infections Front. Microbiol. 2019 10 1057 10.3389/fmicb.2019.01057 31134045 PMC6524401 · DOI
  66. [71]Laurenzi M.A. Siden A. Persson M.A. Norkrans G. Hagberg L. Chiodi F. Cerebrospinal fluid interleukin-6 activity in HIV infection and inflammatory and noninflammatory diseases of the nervous system Clin. Immunol. Immunopathol. 1990 57 233 241 10.1016/0090-1229(90)90037-Q 2208805 · DOI
  67. [72]Shah A. Verma A.S. Patel K.H. Noel R. Rivera-Amill V. Silverstein P.S. Chaudhary S. Bhat H.K. Stamatatos L. Singh D.P. HIV-1 gp120 induces expression of IL-6 through a nuclear factor-kappa B-dependent mechanism: Suppression by gp120 specific small interfering RNA PLoS ONE 2011 6 e21261 10.1371/journal.pone.0021261 21712995 PMC3119684 · DOI
  68. [73]Liu X. Kumar A. Differential signaling mechanism for HIV-1 Nef-mediated production of IL-6 and IL-8 in human astrocytes Sci. Rep. 2015 5 9867 10.1038/srep09867 26075907 PMC4467202 · DOI

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Sorted by citations

Authors
Edara, V. V., Nooka, S., Proulx, J., Stacy, S., Ghorpade, A., & Borgmann, K.
Affiliations
University of North Texas Health Science Center (US)
Corresponding author
  • Ghorpade, Anuja
  • Borgmann, Kathleen
ORCID
Venue
Biomedicines
Publisher
MDPI AG
Published
2020-11-06
Volume
8
Issue
11
Pages
479
ISSN
2227-9059 (ISSN-L)
DOI
10.3390/biomedicines8110479
PMC
PMC7694627
OpenAlex
W3096975252
Cited by
25
References
4
Citations by year
2026: 6 · 2025: 2 · 2024: 2 · 2023: 7 · 2022: 7 · 2021: 1
FWCI
1.45
Type
journal article
Language
en
Open access
Licence
Locations
  • Biomedicines (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • National Institute of Mental Health (R21 MH113452)
  • JES Edwards Foundation of Fort Worth (none)
Topics
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Wnt/β-catenin signaling in development and cancer
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Keywords
β-catenin, Wnt/β-catenin signaling, reactive astrogliosis, HIV-associated neurocognitive disorders, astrocytes, interleukin-6, NF-κB, GSK3β, IL-1β, TNF-α, astrocyte proliferation, astrocyte migration, wound healing, neuroinflammation, MCP-1, interleukin-8

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