Skip to main content

Advertisement

SpringerLink
Log in

Autocrine S100B in astrocytes promotes VEGF-dependent inflammation and oxidative stress and causes impaired neuroprotection

  • Original Article
  • Published:
Cell Biology and Toxicology Aims and scope Submit manuscript

Abstract

Minimal hepatic encephalopathy (MHE) is strongly associated with neuroinflammation. Nevertheless, the underlying mechanism of the induction of inflammatory response in MHE astrocytes remains not fully understood. In the present study, we investigated the effect and mechanism of S100B, a predominant isoform expressed and released from mature astrocytes, on MHE-like neuropathology in the MHE rat model. We discovered that S100B expressions and autocrine were significantly increased in MHE rat brains and MHE rat brain-derived astrocytes. Furthermore, S100B stimulates VEGF expression via the interaction between TLR2 and RAGE in an autocrine manner. S100B-facilitated VEGF autocrine expression further led to a VEGFR2 and COX-2 interaction, which in turn induced the activation of NFƙB, eventually resulting in inflammation and oxidative stress in MHE astrocytes. MHE astrocytes supported impairment of neuronal survival and growth in a co-culture system. To sum up, a comprehensive understanding of the role of S100B-overexpressed MHE astrocyte in MHE pathogenesis may provide insights into the etiology of MHE.

Graphical abstract

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
Figure 7
Figure 8
Figure 9

Similar content being viewed by others

Data availability

The data that support the findings of this study are available from the corresponding author upon reasonable request.

Declarations

Ethics approval and consent to participate

The study was approved by the Ethics Committee of the First Affiliated Hospital of Wenzhou Medical University.

Consent for publication

Not applicable.

Competing interests

The authors declare no competing interests.

Abbreviations

AAALAC:

The Association for Assessment and Accreditation of Laboratory Animal Care International

AD:

Alzheimer’s disease

ANOVA:

One-way analysis of variance

BSA:

Albumin from bovine serum

CNS:

Central nervous system

COX-2:

Cyclooxygenase 2

DAPI:

4′6-Diamidino-2-phenylindole

DMEM:

Dulbecco’s Modified Eagle Medium

DMSO:

Dimethyl sulfoxide

DNAse:

Deoxyribonuclease

EDTA:

Ethylene diamine tetraacetic acid

ELISA:

Enzyme-linked immunosorbent assay

FCS:

Fetal calf serum

GAPDH:

Glyceraldehyde-3-phosphate dehydrogenase

GFAP:

Glial fibrillary acidic protein

HBSS:

Hank’s balanced salt solution

HSC:

Hematopoietic stem cells

IACUC:

Institutional Animal Care and Use Committee

IB:

Immunoblotting

IL-1β:

Interleukin-1β

IP:

Intraperitoneal injection

LTP:

Long-term potentiation

Map 2:

Microtubule-associated protein 2

MHE:

Minimal hepatic encephalopathy

N2A:

Neuroblastoma 2a

NFƙB:

Nuclear factor kappa-B

NOX:

NADPH oxidase

PBS:

Phosphate buffer saline

PDTC:

Pyrrolidinedithiocarbamic acid

PVDF:

Polyvinylidene fluoride

qPCR:

Real-time quantitative PCR

RAGE:

Advanced glycation end product receptor

S100B:

S100 calcium-binding protein B

SDS-PAGE:

Sodium dodecyl sulfate polyacrylamide gel electrophoresis

SiRNA:

Small interfering RNA

TAA:

Thioacetamide

TLR2:

Toll-like receptor 2

TNF-α:

Tumor necrosis factor α

TUNEL:

Transferase dUTP nick end labeling

VEGF:

Vascular endothelial growth factor

VEGFa:

Vascular endothelial growth factor a

VEGFR1:

Vascular endothelial growth factor receptor 1

VEGFR2:

Vascular endothelial growth factor receptor 2

WFT:

Water-finding task

WT :

Wild-type

YM task:

Y-maze task

References

  • Adami C, Bianchi R, Pula G, Donato R. S100B-stimulated NO production by BV-2 microglia is independent of RAGE transducing activity but dependent on RAGE extracellular domain. Biochim Biophys Acta. 2004;1742(1):169–77.

    Article  CAS  PubMed  Google Scholar 

  • Akira S, Uematsu S, Takeuchi O. Pathogen recognition and innate immunity. Cell. 2006;124(4):783–801.

    Article  CAS  PubMed  Google Scholar 

  • Albrecht J, Hilgier W, Zielinska M, Januszewski S, Hesselink M, Quack G. Extracellular concentrations of taurine, glutamate, and aspartate in the cerebral cortex of rats at the asymptomatic stage of thioacetamide-induced hepatic failure: modulation by ketamine anesthesia. Neurochem Res. 2000;25(11):1497–502.

    Article  CAS  PubMed  Google Scholar 

  • Alejandro V, Rocío S, Agustina GT, Gerardo R, Maria Florencia A, Alicia R, Barker PA, Alberto Javier R. S100B protein activates a RAGE-dependent autocrine loop in astrocytes: implications for its role in the propagation of reactive gliosis. J Neurochem. 2014;131(2):190.

    Article  Google Scholar 

  • Amodio P, Montagnese S, Gatta A, Morgan MY. Characteristics of minimal hepatic encephalopathy. Metab Brain Dis. 2004;19(3-4):253–67.

    Article  PubMed  Google Scholar 

  • Araque A, Carmignoto G, Haydon PG. Dynamic signaling between astrocytes and neurons. Annu Rev Physiol. 2001;63(1):795–813.

    Article  CAS  PubMed  Google Scholar 

  • Arumugam T, Simeone DM, Schmidt AM, Logsdon CD. S100P stimulates cell proliferation and survival via receptor for activated glycation end products (RAGE). J Biol Chem. 2004;279(7):5059–65.

    Article  CAS  PubMed  Google Scholar 

  • Aukrust P, Ueland T, Lien E, Bendtzen K, Müller F, Andreassen AK, Nordøy I, Aass H, Espevik T, Simonsen S. Cytokine network in congestive heart failure secondary to ischemic or idiopathic dilated cardiomyopathy ☆. Am J Cardiol. 1999;83(3):376–82.

    Article  CAS  PubMed  Google Scholar 

  • Bagri A, Tessier-Lavigne M. Neuropilins Semaphorin Recept. 2002.

  • Baker PN, Krasnow J, Roberts JM, Yeo KT. Elevated serum levels of vascular endothelial growth factor in patients with preeclampsia ***. Obstet Gynecol. 1995;86(5):815–21.

    Article  CAS  PubMed  Google Scholar 

  • Barr MP, Bouchier-Hayes DJ, Harmey JJ. Vascular endothelial growth factor is an autocrine survival factor for breast tumour cells under hypoxia. Int J Oncol. 2008;32(1):41–8.

    CAS  PubMed  Google Scholar 

  • Basta G, Lazzerini G, Massaro M, Simoncini T, Tanganelli P, Fu C, Kislinger T, Stern DM, Schmidt AM, De Caterina R. Advanced glycation end products activate endothelium through signal-transduction receptor RAGE: a mechanism for amplification of inflammatory responses.%A Basta G. Circulation. 2002;105(7):816–22.

    Article  CAS  PubMed  Google Scholar 

  • Bazan NG. COX-2 as a multifunctional neuronal modulator. Nat Med. 2001;7(4):414–5.

    Article  CAS  PubMed  Google Scholar 

  • Bazan NG. Synaptic lipid signaling: significance of polyunsaturated fatty acids and platelet-activating factor. J Lipid Res. 2003;44(12):2221–33.

    Article  CAS  PubMed  Google Scholar 

  • Beijnum JRV, Buurman WA, Griffioen AW. Convergence and amplification of toll-like receptor (TLR) and receptor for advanced glycation end products (RAGE) signaling pathways via high mobility group B1 (HMGB1). Angiogenesis. 2008;11(1):91–9.

    Article  CAS  PubMed  Google Scholar 

  • Bianchi R, Giambanco I, Donato R. S100B/RAGE-dependent activation of microglia via NF-kappaB and AP-1 Co-regulation of COX-2 expression by S100B, IL-1beta and TNF-alpha. Neurobiol Aging. 2010;31(4):665–77.

    Article  CAS  PubMed  Google Scholar 

  • Bonizzi G, Piette J, Schoonbroodt S, Greimers R, Havard L, Merville MP, Bours V. Reactive oxygen intermediate-dependent NF-κB activation by interleukin-1β requires 5-lipoxygenase or NADPH oxidase activity. Mol Cell Biol. 1999;19(3):1950–60.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Byzova TV, Goldman CK, Pampori N, Thomas KA, Bett A, Shattil SJ, Plow EF. A mechanism for modulation of cellular responses to VEGF : activation of the integrins. Mol Cell. 2000;6(4):851–60.

    CAS  PubMed  Google Scholar 

  • Chavakis T, Bierhaus A, Nawroth PP. RAGE (receptor for advanced glycation end products): a central player in the inflammatory response. Microbes Infect. 2004;6(13):1219–25.

    Article  CAS  PubMed  Google Scholar 

  • Chow J, Ogunshola O, Fan SY, Li Y, Ment LR, Madri JA. Astrocyte-derived VEGF mediates survival and tube stabilization of hypoxic brain microvascular endothelial cells in vitro. Brain Res Dev Brain Res. 2001;130(1):123–32.

    Article  CAS  PubMed  Google Scholar 

  • Danielski M, Ikizler TA, Mcmonagle E, Kane JC, Pupim L, Morrow J, Himmelfarb J. Linkage of hypoalbuminemia, inflammation, and oxidative stress in patients receiving maintenance hemodialysis therapy ☆. Am J Kidney Dis Off J Natl Kidney Found. 2003;42(2):286–94.

    Article  CAS  Google Scholar 

  • Dey A, Maric C, Kaesemeyer WH, Zaharis CZ, Stewart J, Pollock JS, Imig JD. Rofecoxib decreases renal injury in obese Zucker rats. Clin Sci. 2004;107(6):561–70.

    Article  CAS  Google Scholar 

  • Ding S, Wang W, Wang X, Liang Y, Liu L, Ye Y, Yang J, Gao H, Zhuge Q. Dopamine burden triggers neurodegeneration via production and release of TNF-alpha from astrocytes in minimal hepatic encephalopathy. Mol Neurobiol. 2016;53(8):5324–43.

    Article  CAS  PubMed  Google Scholar 

  • Dobrogowska DH, Lossinsky AS, Tarnawski M, Vorbrodt AW. Increased blood-brain barrier permeability and endothelial abnormalities induced by vascular endothelial growth factor. J Neurocytol. 1998;27(3):163–73.

    Article  CAS  PubMed  Google Scholar 

  • Donato R. S100: a multigenic family of calcium-modulated proteins of the EF-hand type with intracellular and extracellular functional roles. Int J Biochem Cell Biol. 2001;33(7):637–68.

    Article  CAS  PubMed  Google Scholar 

  • Gerber HP, Malik AK, Solar GP, Sherman D, Liang XH, Meng G, Hong K, Marsters JC, Ferrara N. VEGF regulates haematopoietic stem cell survival by an internal autocrine loop mechanism. Nature. 2002;417(6892):954–8.

    Article  CAS  PubMed  Google Scholar 

  • Gerlai R, Wojtowicz JM, Marks A, Roder J. Overexpression of a calcium-binding protein, S100 beta, in astrocytes alters synaptic plasticity and impairs spatial learning in transgenic mice. Learn Mem. 1995;2(1):26.

    Article  CAS  PubMed  Google Scholar 

  • Gille H, Kowalski J, Li B, Lecouter J, Moffat B, Zioncheck TF, Pelletier N, Ferrara N. Gille, H. et al. Analysis of biological effects and signaling properties of Flt-1 (VEGFR-1) and KDR (VEGFR-2). A reassessment using novel receptor-specific vascular endothelial growth factor mutants. J. Biol. Chem. 276, 3222-3230. J Biol Chem. 2001;276(5):3222–30.

    Article  CAS  PubMed  Google Scholar 

  • Giuseppe E, Carla C, Giovanni S, Daniele DF, Francesco Paolo DA, Alba R, Gerardo N, Raffaella P, Michela G, Paola I. Enteric glial-derived S100B protein stimulates nitric oxide production in celiac disease. Gastroenterology. 2007;133(3):918–25.

    Article  Google Scholar 

  • Gomes FCA, Spohr T. CLS, Martinez, Neto M: Cross-talk between neurons and glia: highlights on soluble factors. Braz J Med Biol Res. 2001;34(5):611.

    Article  CAS  PubMed  Google Scholar 

  • Harris SG, Padilla J, Koumas L, Ray D, Phipps RP. Prostaglandins as modulators of immunity. Trends Immunol. 2002;23(3):144–50.

    Article  CAS  PubMed  Google Scholar 

  • Heizmann CW. Ca 2+ -Binding S100 proteins in the central nervous system. Neurochem Res. 1999;24(9):1097–100.

    Article  CAS  PubMed  Google Scholar 

  • Hewett SJ, Bell SC, Hewett JA. Contributions of cyclooxygenase-2 to neuroplasticity and neuropathology of the central nervous system. Pharmacol Ther. 2006;112(2):335–57.

    Article  CAS  PubMed  Google Scholar 

  • Hewett SJ, Uliasz TF, Vidwans AS, Hewett JA. Cyclooxygenase-2 contributes to N-methyl-D-aspartate-mediated neuronal cell death in primary cortical cell culture. J Pharmacol Exp Ther. 2000;293(2):417–25.

    CAS  PubMed  Google Scholar 

  • Hiscott J, Marois J, Garoufalis J, D'Addario M, Roulston A, Kwan I, Pepin N, Lacoste J, Nguyen H, Bensi G. Characterization of a functional NF-kappa B site in the human interleukin 1 beta promoter: evidence for a positive autoregulatory loop. Mol Cell Biol. 1993;13(10):6231–40.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Ho L, Pieroni C, Winger D, Purohit DP, Aisen PS, Pasinetti GM. Regional distribution of cyclooxygenase-2 in the hippocampal formation in Alzheimer's disease. J Neurosci Res. 1999;57(3):295–303.

    Article  CAS  PubMed  Google Scholar 

  • Hofmann MA, Drury S, ., Fu C, ., Qu W, ., Taguchi A, ., Lu Y, ., Avila C, ., Kambham N, ., Bierhaus A, ., Nawroth P, . RAGE mediates a novel proinflammatory axis: a central cell surface receptor for S100/calgranulin polypeptides. Cell 1999a, 97(7):889-901.

    Article  CAS  PubMed  Google Scholar 

  • Hofmann MA, Drury S, Fu C, Qu W, Taguchi A, Lu Y, Avila C, Kambham N, Bierhaus A, Nawroth P. RAGE mediates a novel proinflammatory axis : a central cell surface receptor for S100/calgranulin polypeptides. Cell. 1999b;97(7):889–901.

    Article  CAS  PubMed  Google Scholar 

  • Howes KA, Liu Y, Dunaief JL, Milam A, Frederick JM, Marks A, Baehr W. Receptor for advanced glycation end products and age-related macular degeneration. Invest Ophthalmol Vis Sci. 2015;45(10):3713.

    Article  Google Scholar 

  • Hu J, Van Eldik LJ. S100 beta induces apoptotic cell death in cultured astrocytes via a nitric oxide-dependent pathway. Biochim Biophys Acta. 1996;1313(3):239.

    Article  PubMed  Google Scholar 

  • Huttunen HJ, Fages C, Rauvala H. Receptor for advanced glycation end products (RAGE)-mediated neurite outgrowth and activation of NF-κB require the cytoplasmic domain of the receptor but different downstream signaling pathways. J Biol Chem. 1999;274(28):19919–24.

    Article  CAS  PubMed  Google Scholar 

  • Iadecola C, Niwa K, Nogawa S, Zhao X, Nagayama M, Araki E, Morham S, Ross ME. Reduced susceptibility to ischemic brain injury and N-methyl-D-aspartate-mediated neurotoxicity in cyclooxygenase-2-deficient mice. Proc Natl Acad Sci U S A. 2001;98(3):1294–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kanner AA, Marchi N, Fazio V, Mayberg MR, Koltz MT, Siomin V, Stevens GH, Masaryk T, Aumayr B, Vogelbaum MA, et al. Serum S100beta: a noninvasive marker of blood-brain barrier function and brain lesions. Cancer. 2003;97(11):2806–13.

    Article  CAS  PubMed  Google Scholar 

  • Karanfilian BV, Park T, Senatore F, Rustgi VK. Minimal hepatic encephalopathy. Clin Liver Dis. 2020;24(2):209–18.

    Article  PubMed  Google Scholar 

  • Kaur C, ., Sivakumar V, ., Zhang Y, ., Ling EA: Hypoxia-induced astrocytic reaction and increased vascular permeability in the rat cerebellum. Glia 2010, 54(8):826-839.

    Article  Google Scholar 

  • Kawasumi M, Chiba T, Yamada M, Miyamae-Kaneko M, Matsuoka M, Nakahara J, Tomita T, Iwatsubo T, Kato S, Aiso S, et al. Targeted introduction of V642I mutation in amyloid precursor protein gene causes functional abnormality resembling early stage of Alzheimer's disease in aged mice. Eur J Neurosci. 2004;19(10):2826–38.

    Article  PubMed  Google Scholar 

  • Khaper N, ., Singal PK: Modulation of oxidative stress by a selective inhibition of angiotensin II type 1 receptors in MI rats. J Am Coll Cardiol 2001, 37(5):1461-1466.

    Article  CAS  PubMed  Google Scholar 

  • Kidambi S, Lee I, Chan C. Primary neuron/astrocyte co-culture on polyelectrolyte multilayer films: a template for studying astrocyte-mediated oxidative stress in neurons. Adv Funct Mater. 2010;18(2):294–301.

    Article  Google Scholar 

  • Koprnová J, Svetlanský I, Babel'A R, Bilíková E, Hanzen J, Zuscáková IJ, Mílovský V, Masár O, Kovacicová G, Gogová M. Prospective study of antibacterial susceptibility, risk factors and outcome of 157 episodes of Acinetobacter baumannii bacteremia in 1999 in Slovakia. Scand J Infect Dis. 2001;33(12):891.

    Article  PubMed  Google Scholar 

  • Lee TH, Seng S, Sekine M, Hinton C, Fu Y, Avraham HK, Avraham S. Vascular endothelial growth factor mediates intracrine survival in human breast carcinoma cells through internally expressed VEGFR1/FLT1. PLoS Med. 2007;4(6):e186.

    Article  PubMed  PubMed Central  Google Scholar 

  • Li Y, Barger SW, Ling L, Mrak RE, Griffin WST. S100 induction of the proinflammatory cytokine interleukin-6 in neurons&nbsp. J Neurochem. 2010;74(1):143–50.

    Google Scholar 

  • Lichtenberger BM, Tan PK, Niederleithner H, Ferrara N, Petzelbauer P, Sibilia M. Autocrine VEGF signaling synergizes with EGFR in tumor cells to promote epithelial cancer development. Cell. 2010;140(2):268–79.

    Article  CAS  PubMed  Google Scholar 

  • Marshak DR, Pesce SA. Increased S100β neurotrophic activity in Alzheimer's disease temporal lobe. Neurobiol Aging. 1992;13(1):1–7.

    Article  CAS  PubMed  Google Scholar 

  • Masakiyo S, Hitoshi M, Ken-Ichi Y, Tomoyuki O, Yoshihiko S, Akira M, Toshihiko H, Ken K, Nam-Ho H. TIRAP, an adaptor protein for TLR2/4, transduces a signal from RAGE phosphorylated upon ligand binding. PLoS One. 2011;6(8):e23132.

    Article  Google Scholar 

  • Matsui T, Mori T, Tateishi N, Kagamiishi Y, Satoh S, Katsube N, Morikawa E, Morimoto T, Ikuta F, Asano T. Astrocytic activation and delayed infarct expansion after permanent focal ischemia in rats. Part I: Enhanced astrocytic synthesis of S-100β in the periinfarct area precedes delayed infarct expansion. J Cereb Blood Flow Metab. 2002;22(6):711–22.

    Article  CAS  PubMed  Google Scholar 

  • McGeer PL, McGeer EG. The inflammatory response system of brain: implications for therapy of Alzheimer and other neurodegenerative diseases. Brain Res Brain Res Rev. 1995;21(2):195–218.

    Article  CAS  PubMed  Google Scholar 

  • McGeer PL, McGeer EG. Inflammation and the degenerative diseases of aging. Ann N Y Acad Sci. 2004;1035:104–16.

    Article  CAS  PubMed  Google Scholar 

  • Miettinen S, Fusco FR, Yrjänheikki J, Keinänen R, Hirvonen T, Roivainen R, Närhi M, Hökfelt T, Koistinaho J. Spreading depression and focal brain ischemia induce cyclooxygenase-2 in cortical neurons through N-methyl-D-aspartic acid-receptors and phospholipase A2. Proc Natl Acad Sci U S A. 1997;94(12):6500–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Minghetti L. Cyclooxygenase-2 (COX-2) in inflammatory and degenerative brain diseases. J Neuropathol Exp Neurol. 2004;63(9):901–10.

    Article  CAS  PubMed  Google Scholar 

  • Minghetti L. Role of COX-2 in inflammatory and degenerative brain diseases. Subcell Biochem. 2007;42:127–41.

    Article  PubMed  Google Scholar 

  • Miyamoto K, Khosrof S, Bursell SE, Moromizato Y, Aiello LP, Ogura Y, Adamis AP. Vascular endothelial growth factor (VEGF)-induced retinal vascular permeability is mediated by intercellular adhesion molecule-1 (ICAM-1). Am J Pathol. 2000;156(5):1733.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Montoliu C, Piedrafita B, Serra MA, del Olmo JA, Ferrandez A, Rodrigo JM, Felipo V. Activation of soluble guanylate cyclase by nitric oxide in lymphocytes correlates with minimal hepatic encephalopathy in cirrhotic patients. J Mol Med. 2007;85(3):237–45.

    Article  CAS  PubMed  Google Scholar 

  • Mousa KK, Louise J, Ogg GS, Damo X, Liew FY. TLR2 is expressed on activated T cells as a costimulatory receptor. Proc Natl Acad Sci U S A. 2004;101(9):3029–34.

    Article  Google Scholar 

  • Mrak RE. C WSTGB: The role of activated astrocytes and of the neurotrophic cytokine S100B in the pathogenesis of Alzheimer’s disease. Neurobiol Aging. 2001;22(6):915–22.

    Article  CAS  PubMed  Google Scholar 

  • Mrak RE, Sheng JG, Griffin WS. Correlation of astrocytic S100 beta expression with dystrophic neurites in amyloid plaques of Alzheimer's disease. J Neuropathol Exp Neurol. 1996;55(3):273.

    Article  CAS  PubMed  Google Scholar 

  • Müller HW, Seifert W. A neurotrophic factor (NTF) released from primary glial cultures supports survival and fiber outgrowth of cultured hippocampal neurons. J Neurosci Res. 1982;8(2-3):195.

    Article  PubMed  Google Scholar 

  • Nakayama M, Uchimura K, Zhu RL, Nagayama T, Rose ME, Stetler RA, Isakson PC, Chen J, Graham SH. Cyclooxygenase-2 inhibition prevents delayed death of CA1 hippocampal neurons following global ischemia. Proc Natl Acad Sci U S A. 1998;95(18):10954–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Neeper M, ., Schmidt AM, Brett J, ., Yan SD, Wang F, ., Pan YC, Elliston K, ., Stern D, ., Shaw A, . Cloning and expression of a cell surface receptor for advanced glycosylation end products of proteins. J Biol Chem 1992, 267(21):14998-15004.

    Article  CAS  PubMed  Google Scholar 

  • Obrosova IG, Drel VR, Kumagai AK, Szábo C, ., Pacher P, ., Stevens MJ: Early diabetes-induced biochemical changes in the retina: comparison of rat and mouse models. Diabetologia 2006, 49(10):2525-2533.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ohba T, Cates JM, Cole HA, Slosky DA, Haro H, Ando T, Schwartz HS, Schoenecker JG. Autocrine VEGF/VEGFR1 signaling in a subpopulation of cells associates with aggressive osteosarcoma. Mol Cancer Res: MCR. 2014;12(8):1100–11.

    Article  CAS  PubMed  Google Scholar 

  • Perkins ND. Integrating cell-signalling pathways with NF-kappaB and IKK function. Nat Rev Mol Cell Biol. 2007;8(1):49–62.

    Article  CAS  PubMed  Google Scholar 

  • Ranuncolo SM, Ladeda V, Gorostidy S, Morandi A, Varela M, Lastiri J, Loria D, Del AR, Joffé EB, Pallotta G. Expression of CD44s and CD44 splice variants in human melanoma. Oncol Rep. 2002;9(1):51–6.

    PubMed  Google Scholar 

  • Reeves RH, Yao J, Crowley MR, Buck S, Zhang X, Yarowsky P, Gearhart JD, Hilt DC. Astrocytosis and axonal proliferation in the hippocampus of S100b transgenic mice. Proc Natl Acad Sci U S A. 1994;91(12):5359–63.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ronaldson PT, Davis TP. Blood-brain barrier integrity and glial support: mechanisms that can be targeted for novel therapeutic approaches in stroke. Curr Pharm Des 2012;18(25).

  • Saban R, Simpson C, Davis CA, Dozmorov I, Maier J, Fowler B, Ihnat MA, Hurst RE, Wershil BK, Saban MR: Transcription factor network downstream of protease activated receptors (PARs) modulating mouse bladder inflammation. BMC Immunol 8,1(2007-08-17) 2007, 8(1):17.

  • Saleh A, Kamel L, Ghali A, Ismail A, El Khayat H. Serum levels of astroglial S100-beta and neuron-specific enolase in hepatic encephalopathy patients. East Mediterr Health J. 2007;13(5):1114–23.

    Article  CAS  PubMed  Google Scholar 

  • Santos SC, Dias S. Internal and external autocrine VEGF/KDR loops regulate survival of subsets of acute leukemia through distinct signaling pathways. Blood. 2004;103(10):3883–9.

    Article  CAS  PubMed  Google Scholar 

  • Schreck R, Albermann K, Baeuerle PA. Nuclear factor kappa B: an oxidative stress-responsive transcription factor of eukaryotic cells (a review). Free Radic Res Commun. 1992;17(4):221–37.

    Article  CAS  PubMed  Google Scholar 

  • Scotto C, Mély Y, Ohshima H, Garin J, Cochet C, Chambaz E, Baudier J. Cysteine oxidation in the mitogenic S100B protein leads to changes in phosphorylation by catalytic CKII-alpha subunit. J Biol Chem. 1998;273(7):3901–8.

    Article  CAS  PubMed  Google Scholar 

  • Shim JW, Madsen JR. VEGF signaling in neurological disorders. Int J Mol Sci. 2018;19(1):275.

    Article  PubMed  PubMed Central  Google Scholar 

  • Shin YJ, Choi JS, Choi JY, Hou Y, Cha JH, Chun MH, Lee MY. Induction of vascular endothelial growth factor receptor-3 mRNA in glial cells following focal cerebral ischemia in rats. J Neuroimmunol. 2010;229(1):81–90.

    Article  CAS  PubMed  Google Scholar 

  • Smith CJ, Zhang Y, ., Koboldt CM, Muhammad J, ., Zweifel BS, Shaffer A, ., Talley JJ, Masferrer JL, Seibert K, ., Isakson PC: Pharmacological analysis of cyclooxygenase-1 in inflammation. Proc Natl Acad Sci U S A 1998, 95(22):13313-13318.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sonia MR. Avenda?O MS, García-Redondo AB, Yolanda A, Andrea A, Pérez-Girón JV, Laura GR, Vanesa E, Redondo JM, Alonso MJ: Reciprocal relationship between reactive oxygen species and cyclooxygenase-2 and vascular dysfunction in hypertension. Antioxid Redox Signal. 2013;18(1):51–65.

    Article  Google Scholar 

  • Sophie N, Johanne B, Annie J, Thérèse P. Changes in expression of vascular endothelial growth factor and its receptors in neonatal hypoxia-induced pulmonary hypertension. Pediatr Res. 2005;58(2):199–205.

    Article  Google Scholar 

  • Sun BD, Liu HM, Nie SN. S100B protein in serum is elevated after global cerebral ischemic injury. World J Emerg Med. 2013;4(3):165–8.

    Article  PubMed  PubMed Central  Google Scholar 

  • Tian J, Avalos A, Mao S, Chen B, Senthil K, Wu H, Parroche P, Drabic S, Golenbock D, Sirois C. Toll-like receptor 9-dependent activation by DNA-containing immune complexes is mediated by HMGB1 and RAGE. Nat Immunol. 2007;8(5):487–96.

    Article  CAS  PubMed  Google Scholar 

  • Tomaselli KJ, Neugebauer KM, Bixby JL, Lilien J, Reichard LF. N-cadherin and integrins: Two receptor systems that mediate neuronal process outgrowth on astrocyte surfaces. Neuron. 1988;1(1):33–43.

    Article  CAS  PubMed  Google Scholar 

  • Tsoporis JN, Marks A, Haddad A, Dawood F, Liu PP, Parker TG. S100B expression modulates left ventricular remodeling after myocardial infarction in mice. Circulation. 2005;111(5):598–606.

    Article  CAS  PubMed  Google Scholar 

  • Uwe S. NF-kappaB in critical diseases: a bad guy? Intensive Care Med. 2003;29(11):1873.

    Article  Google Scholar 

  • Van Eldik LJ, Wainwright MS. The Janus face of glial-derived S100B: beneficial and detrimental functions in the brain. Restor Neurol Neurosci. 2003;21(3-4):97–108.

    PubMed  Google Scholar 

  • Van Eldik LJ, Zimmer DB. Secretion of S-100 from rat C6 glioma cells. Brain Res. 1987;436(2):367–70.

    Article  PubMed  Google Scholar 

  • Wainwright MS, Craft JM, Griffin WST, Alexander M, Jose P, Padgett KR, Eldik LJ, Van: Increased susceptibility of S100B transgenic mice to perinatal hypoxia-ischemia. Ann Neurol 2010, 56(1):61-67.

  • Wang DD, Bordey A. The astrocyte odyssey. Prog Neurobiol. 2008;86(4):342–67.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Weis SM, Cheresh DA. Pathophysiological consequences of VEGF-induced vascular permeability. Nature. 2005;437(7058):497–504.

    Article  CAS  PubMed  Google Scholar 

  • Wilder PT, Varney KM, Weiss MB, Gitti RK, Weber DJ. Solution structure of zinc- and calcium-bound rat S100B as determined by nuclear magnetic resonance spectroscopy. Biochemistry. 2005;44(15):5690.

    Article  CAS  PubMed  Google Scholar 

  • Yamada M, Chiba T, Sasabe J, Nawa M, Tajima H, Niikura T, Terashita K, Aiso S, Kita Y, Matsuoka M, et al. Implanted cannula-mediated repetitive administration of Abeta25-35 into the mouse cerebral ventricle effectively impairs spatial working memory. Behav Brain Res. 2005;164(2):139–46.

    Article  CAS  PubMed  Google Scholar 

  • Yan SD, Chen X, Fu J, Chen M, Zhu H, Roher A, Slattery T, Zhao L, Nagashima M, Morser J. RAGE and amyloid-|[beta]| peptide neurotoxicity in Alzheimer's disease. Nature. 1996;382(6593):685–91.

    Article  CAS  PubMed  Google Scholar 

  • Yan SD, Schmidt AM, Anderson GM, Zhang J, Brett J, Zou YS, Pinsky D, Stern D. Enhanced cellular oxidant stress by the interaction of advanced glycation end products with their receptors/binding proteins. J Biol Chem. 1994;269(13):9889–97.

    Article  CAS  PubMed  Google Scholar 

  • Zimmer DB, Cornwall EH, Landar A, Song W. The S100 protein family: history, function, and expression. Brain Res Bull. 1995;37(4):417.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

We thank Dr. Haoqi Ni for optimizing the image analysis method. We thank Dr. Yangping Shentu for technical supports. We thank Dr. Yunchang Mo for critical reading of the manuscript.

Funding

This study was supported by Basic Scientific Research Projects of Wenzhou science and Technology Bureau (Y20180076), Natural Science Foundation of Zhejiang Province (LY21H030012), and Natural Science Foundation of China (81671042, 81300308).

Author information

Author notes

  1. Saidan Ding, Chengde Wang, Weikan Wang, He Yu, Baihui Chen and Leping Liu contributed equally to this work.

Authors and Affiliations

  1. Central Laboratory, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, Zhejiang, China

    Saidan Ding, He Yu, Baihui Chen, Leping Liu, Minxue Zhang & Yan Lang

  2. Neurosurgery department, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, Zhejiang, China

    Chengde Wang

  3. Department of Microbiology, Immunology and Genetics, University of North Texas Health Science Center, Fort Worth, TX, 76107, USA

    Weikan Wang

Authors
  1. Saidan Ding
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Chengde Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Weikan Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. He Yu
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Baihui Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Leping Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Minxue Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Yan Lang
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Saidan Ding and Chende Wang supervised the entire project, designed the research, analyzed the data, and critically revised the manuscript. Yan Lang and Baihui Chen conceived and designed the experiments, performed the research interpreted, analyzed the data, and wrote the manuscript. Minxue Zhang and Weikan Wang conceived and designed the experiments, interpreted and analyzed the data, and supervised all the experimental procedures. Leping Liu and He Yu performed the research and analyzed the data. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Saidan Ding.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

1. S100B expressions were significantly increased in MHE rat brains and MHE rat brain-derived astrocytes.

2. S100B stimulates VEGF expression via the interaction between TLR2 and RAGE in an autocrine manner, which in turn induced VEGFR2 and COX-2 interaction, eventually resulting in inflammation and oxidative stress in MHE astrocytes.

3. MHE astrocytes supported impairment of neuronal growth.

Supplementary Information

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Ding, S., Wang, C., Wang, W. et al. Autocrine S100B in astrocytes promotes VEGF-dependent inflammation and oxidative stress and causes impaired neuroprotection. Cell Biol Toxicol 39, 1–25 (2023). https://doi.org/10.1007/s10565-021-09674-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10565-021-09674-1

Keywords

Search

Navigation