Skip to main content

Advertisement

SpringerLink
Log in

Resistin-Inhibited Neural Stem Cell-Derived Astrocyte Differentiation Contributes to Permeability Destruction of the Blood–Brain Barrier

  • Original Paper
  • Published:
Neurochemical Research Aims and scope Submit manuscript

Abstract

Neuroinflammation is an important part of the development of neurodegenerative diseases such as Alzheimer’s disease (AD), Parkinson’s and amyotrophic lateral sclerosis. Inflammatory factors destroy the balance of the microenvironment, which results in changes in neural stem cell differentiation and proliferation behaviour. However, the mechanism underlying inflammatory factor-induced NSC behavioural changes is not clear. Resistin is a proinflammatory and adipogenic factor and is involved in several human pathology processes. The neural stem cell microenvironment changes when the concentration of resistin in the brain during an inflammatory response disease increases. In the present study, we explored the effect and mechanism of resistin on the proliferation and differentiation of neural stem cells. We found that intracerebroventricular injection of resistin induced a decrease in GFAP-positive cells in mice by influencing NSC differentiation. Resistin significantly decreased TEER and increased permeability in an in vitro blood–brain barrier model, which is consistent with the results of an HBMEC-astrocyte coculture system. Resistin-inhibited astrocyte differentiation is mediated through TLR4 on neural stem cells. To our knowledge, this is the first study reporting the effect of resistin on neural stem cells. Our findings shed light on resistin-involved neural stem cell degeneration mechanisms.

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

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7

Similar content being viewed by others

References

  1. Członkowska A, Kurkowska-Jastrzębska I (2011) Inflammation and gliosis in neurological diseases–clinical implications. J Neuroimmunol 231(1–2):78–85

    PubMed  Google Scholar 

  2. McGeer PL, Itagaki S, McGeer EG (1988) Expression of the histocompatibility glycoprotein HLA-DR in neurological disease. Acta Neuropathol 76(6):550–557

    CAS  PubMed  Google Scholar 

  3. Imamura K, Hishikawa N, Ono K, Suzuki H, Sawada M, Nagatsu T, Yoshida M, Hashizume Y (2005) Cytokine production of activated microglia and decrease in neurotrophic factors of neurons in the hippocampus of Lewy body disease brains. Acta Neuropathol 109(2):141–150

    CAS  PubMed  Google Scholar 

  4. Mrak RE, Griffin WS (2007) Common inflammatory mechanisms in Lewy body disease and Alzheimer disease. J Neuropathol Exp Neurol 66(8):683–686

    CAS  PubMed  Google Scholar 

  5. Clarke DL, Johansson CB, Wilbertz J, Veress B, Nilsson E, Karlström H, Lendahl U, Frisén J (2000) Generalized potential of adult neural stem cells. Science 288(5471):1660–1663

    CAS  PubMed  Google Scholar 

  6. Altman J, Das GD (1965) Post-natal origin of microneurones in the rat brain. Nature 207(5000):953–956

    CAS  PubMed  Google Scholar 

  7. Altman J (1969) Autoradiographic and histological studies of postnatal neurogenesis. IV. Cell proliferation and migration in the anterior forebrain, with special reference to persisting neurogenesis in the olfactory bulb. J Comp Neurol 137(4):433–457

    CAS  PubMed  Google Scholar 

  8. Kempermann G, van Praag H, Gage FH (2000) Activity-dependent regulation of neuronal plasticity and self repair. Prog Brain Res 127:35–48

    CAS  PubMed  Google Scholar 

  9. Kempermann G, Gast D, Kronenberg G, Yamaguchi M, Gage FH (2003) Early determination and long-term persistence of adult-generated new neurons in the hippocampus of mice. Development 130(2):391–399

    CAS  PubMed  Google Scholar 

  10. Seidenfaden R, Desoeuvre A, Bosio A, Virard I, Cremer H (2006) Glial conversion of SVZ-derived committed neuronal precursors after ectopic grafting into the adult brain. Mol Cell Neurosci 32(1–2):187–198

    CAS  PubMed  Google Scholar 

  11. Palmer TD, Willhoite AR, Gage FH (2000) Vascular niche for adult hippocampal neurogenesis. J Comp Neurol 425(4):479–494

    CAS  PubMed  Google Scholar 

  12. Oatley JM, Brinster RL (2012) The germline stem cell niche unit in mammalian testes. Physiol Rev 92(2):577–595

    CAS  PubMed  Google Scholar 

  13. Chen S, Lewallen M, Xie T (2013) Adhesion in the stem cell niche: biological roles and regulation. Development 140(2):255–265

    CAS  PubMed  PubMed Central  Google Scholar 

  14. Ghiaur G, Yegnasubramanian S, Perkins B, Gucwa JL, Gerber JM, Jones RJ (2013) Regulation of human hematopoietic stem cell self-renewal by the microenvironment’s control of retinoic acid signaling. Proc Natl Acad Sci USA 110(40):16121–16126

    CAS  PubMed  PubMed Central  Google Scholar 

  15. Mirshekar-Syahkal B, Fitch SR, Ottersbach K (2014) Concise review: from greenhouse to garden: the changing soil of the hematopoietic stem cell microenvironment during development. Stem Cells 32(7):1691–1700

    CAS  PubMed  Google Scholar 

  16. Jung HS, Park KH, Cho YM, Chung SS, Cho HJ, Cho SY, Kim SJ, Kim SY, Lee HK, Park KS (2006) Resistin is secreted from macrophages in atheromas and promotes atherosclerosis. Cardiovasc Res 69(1):76–85

    CAS  PubMed  Google Scholar 

  17. Kusminski CM, McTernan PG, Kumar S (2005) Role of resistin in obesity, insulin resistance and Type II diabetes. Clin Sci (London) 109(3):243–256

    CAS  Google Scholar 

  18. Bokarewa M, Nagaev I, Dahlberg L, Smith U, Tarkowski A (2005) Resistin, an adipokine with potent proinflammatory properties. J Immunol 174(9):5789–5795

    CAS  PubMed  Google Scholar 

  19. Demirci S, Aynalı A, Demirci K, Demirci S, Arıdoğan BC (2017) The serum levels of resistin and its relationship with other proinflammatory cytokines in patients with Alzheimer’s Disease. Clin Psychopharmacol Neurosci 15(1):59–63

    CAS  PubMed  PubMed Central  Google Scholar 

  20. Qi Y, Jia K, Zhang DQ, Li T, Li LM, Zhang LJ, Wang J, Gao CL, Sun LS, Shi FD, Yang L (2016) Increased resistin levels in the serum and cerebrospinal fluid of patients with neuromyelitis optica. Clin Chim Acta 456:176–179

    CAS  PubMed  Google Scholar 

  21. Stins MF, Gilles F, Kim KS (1997) Selective expression of adhesion molecules on human brain microvascular endothelial cells. J Neuroimmunol 76(1–2):81–90

    CAS  PubMed  Google Scholar 

  22. Zhang H, Zhang S, Zhang J, Liu D, Wei J, Fang W, Zhao W, Chen Y, Shang D (2018) ZO-1 expression is suppressed by GM-CSF via miR-96/ERG in brain microvascular endothelial cells. J Cereb Blood Flow Metab 38(5):809–822

    CAS  PubMed  Google Scholar 

  23. Vandenhaute E, Culot M, Gosselet F, Dehouck L, Godfraind C, Franck M, Plouët J, Cecchelli R, Dehouck MP, Ruchoux MM (2012) Brain pericytes from stress-susceptible pigs increase blood-brain barrier permeability in vitro. Fluids Barriers CNS 9(1):11

    PubMed  PubMed Central  Google Scholar 

  24. Cullen DK, Simon CM, LaPlaca MC (2007) Strain rate-dependent induction of reactive astrogliosis and cell death in three-dimensional neuronal-astrocytic co-cultures. Brain Res 1158:103–115

    CAS  PubMed  PubMed Central  Google Scholar 

  25. Guérette D, Khan PA, Savard PE, Vincent M (2007) Molecular evolution of type VI intermediate filament proteins. BMC Evol Biol 7:164

    PubMed  PubMed Central  Google Scholar 

  26. Michalczyk K, Ziman M (2005) Nestin structure and predicted function in cellular cytoskeletal organisation. Histol Histopathol 20(2):665–671

    CAS  PubMed  Google Scholar 

  27. Bravo R, Frank R, Blundell PA, Macdonald-Bravo H (1987) Cyclin/PCNA is the auxiliary protein of DNA polymerase-delta. Nature 326(6112):515–517

    CAS  PubMed  Google Scholar 

  28. Yan SS, Wu ZY, Zhang HP, Furtado G, Chen X, Yan SF, Schmidt AM, Brown C, Stern A, LaFaille J, Chess L, Stern DM, Jiang H (2003) Suppression of experimental autoimmune encephalomyelitis by selective blockade of encephalitogenic T-cell infiltration of the central nervous system. Nat Med 9(3):287–293

    CAS  PubMed  Google Scholar 

  29. Walder S, Ferretti P (2004) Distinct neural precursors in the developing human spinal cord. Int J Dev Biol 48(7):671–674

    CAS  PubMed  Google Scholar 

  30. Gilyarov AV (2008) Nestin in central nervous system cells. Neurosci Behav Physiol 38(2):165–169

    CAS  PubMed  Google Scholar 

  31. Janabi M, Yamashita S, Hirano K, Sakai N, Hiraoka H, Matsumoto K, Zhang Z, Nozaki S, Matsuzawa Y (2000) Oxidized LDL-induced NF-kappa B activation and subsequent expression of proinflammatory genes are defective in monocyte-derived macrophages from CD36-deficient patients. Arterioscler Thromb Vasc Biol 20(8):1953–1960

    CAS  PubMed  Google Scholar 

  32. McGilvray ID, Serghides L, Kapus A, Rotstein OD, Kain KC (2000) Nonopsonic monocyte/macrophage phagocytosis of Plasmodium falciparum-parasitized erythrocytes: a role for CD36 in malarial clearance. Blood 96(9):3231–3240

    CAS  PubMed  Google Scholar 

  33. Bamberger ME, Harris ME, McDonald DR, Husemann J, Landreth GE (2003) A cell surface receptor complex for fibrillar beta-amyloid mediates microglial activation. J Neurosci 23(7):2665–2674

    CAS  PubMed  PubMed Central  Google Scholar 

  34. Amiel E, Alonso A, Uematsu S, Akira S, Poynter ME, Berwin B (2009) Pivotal advance: toll-like receptor regulation of scavenger receptor-A-mediated phagocytosis. J Leukoc Biol 85(4):595–605

    CAS  PubMed  Google Scholar 

  35. Fang H, Chen J, Lin S, Wang P, Wang Y, Xiong X, Yang Q (2014) CD36-mediated hematoma absorption following intracerebral hemorrhage: negative regulation by TLR4 signaling. J Immunol 192(12):5984–5992

    CAS  PubMed  PubMed Central  Google Scholar 

  36. Zheng Z, Ai J, Li XA (2014) Scavenger receptor class B type I and immune dysfunctions. Curr Opin Endocrinol Diabetes Obes 21(2):121–128

    PubMed  Google Scholar 

  37. Bao Y, Qin L, Kim E, Bhosle S, Guo H, Febbraio M, Haskew-Layton RE, Ratan R, Cho S (2012) CD36 is involved in astrocyte activation and astroglial scar formation. J Cereb Blood Flow Metab 32(8):1567–1577

    CAS  PubMed  PubMed Central  Google Scholar 

  38. Gan AM, Butoi ED, Manea A, Simion V, Stan D, Parvulescu MM, Calin M, Manduteanu I, Simionescu M (2013) Inflammatory effects of resistin on human smooth muscle cells: up-regulation of fractalkine and its receptor, CX3CR1 expression by TLR4 and Gi-protein pathways. Cell Tissue Res 351(1):161–174

    CAS  PubMed  Google Scholar 

  39. Hsieh YY, Shen CH, Huang WS, Chin CC, Kuo YH, Hsieh MC, Yu HR, Chang TS, Lin TH, Chiu YW, Chen CN, Kuo HC, Tung SY (2014) Resistin-induced stromal cell-derived factor-1 expression through Toll-like receptor 4 and activation of p38 MAPK/ NFκB signaling pathway in gastric cancer cells. J Biomed Sci 21:59

    PubMed  PubMed Central  Google Scholar 

  40. Stefanova N, Reindl M, Neumann M, Kahle PJ, Poewe W, Wenning GK (2007) Microglial activation mediates neurodegeneration related to oligodendroglial alpha-synucleinopathy: implications for multiple system atrophy. Mov Disord 22(15):2196–2203

    PubMed  Google Scholar 

  41. Stamatovic SM, Keep RF, Andjelkovic AV (2008) Brain endothelial cell-cell junctions: how to “open” the blood brain barrier. Curr Neuropharmacol 6(3):179–192

    CAS  PubMed  PubMed Central  Google Scholar 

  42. Argaw AT, Asp L, Zhang J, Navrazhina K, Pham T, Mariani JN, Mahase S, Dutta DJ, Seto J, Kramer EG, Ferrara N, Sofroniew MV, John GR (2012) Astrocyte-derived VEGF-A drives blood-brain barrier disruption in CNS inflammatory disease. J Clin Invest 122(7):2454–2468

    CAS  PubMed  PubMed Central  Google Scholar 

  43. Muruganandam A, Herx LM, Monette R, Durkin JP, Stanimirovic DB (1997) Development of immortalized human cerebromicrovascular endothelial cell line as an in vitro model of the human blood-brain barrier. FASEB J 11(13):1187–1197

    CAS  PubMed  Google Scholar 

  44. Covacu R, Brundin L (2015) Effects of neuroinflammation on neural stem cells. Neuroscientist 23:37–39

    Google Scholar 

  45. Al-Suhaimi EA, Shehzad A (2013) Leptin, resistin and visfatin: the missing link between endocrine metabolic disorders and immunity. Eur J Med Res 18:12

    CAS  PubMed  PubMed Central  Google Scholar 

  46. Kos K, Harte AL, da Silva NF, Tonchev A, Chaldakov G, James S, Snead DR, Hoggart B, O’Hare JP, McTernan PG, Kumar S (2007) Adiponectin and resistin in human cerebrospinal fluid and expression of adiponectin receptors in the human hypothalamus. J Clin Endocrinol Metab 92(3):1129–1136

    CAS  PubMed  Google Scholar 

  47. Berghoff M, Hochberg A, Schmid A, Schlegel J, Karrasch T, Kaps M, Schäffler A (2016) Quantification and regulation of the adipokines resistin and progranulin in human cerebrospinal fluid. Eur J Clin Invest 46(1):15–26

    CAS  PubMed  Google Scholar 

  48. Alsuhaymi N, Habeeballah H, Stebbing MJ, Badoer E (2017) High fat diet decreases neuronal activation in the brain induced by resistin and leptin. Front Physiol 8:867

    PubMed  PubMed Central  Google Scholar 

  49. Kusminski CM, da Silva NF, Creely SJ, Fisher FM, Harte AL, Baker AR, Kumar S, McTernan PG (2007) The in vitro effects of resistin on the innate immune signaling pathway in isolated human subcutaneous adipocytes. J Clin Endocrinol Metab 92(1):270–276

    CAS  PubMed  Google Scholar 

  50. Fuster-Matanzo A, Llorens-Martín M, Hernández F, Avila J (2013) Role of neuroinflammation in adult neurogenesis and Alzheimer disease: therapeutic approaches. Mediators Inflamm 2013:260925

    PubMed  PubMed Central  Google Scholar 

  51. Sofroniew MV (2015) Astrocyte barriers to neurotoxic inflammation. Nat Rev Neurosci 16(5):249–263

    CAS  PubMed  PubMed Central  Google Scholar 

  52. Yao Y, Chen ZL, Norris EH, Strickland S (2014) Astrocytic laminin regulates pericyte differentiation and maintains blood brain barrier integrity. Nat Commun 5:3413

    PubMed  Google Scholar 

  53. Zlokovic BV (2008) The blood-brain barrier in health and chronic neurodegenerative disorders. Neuron 57(2):178–201

    CAS  PubMed  Google Scholar 

  54. Shang S, Yang YM, Zhang H, Tian L, Jiang JS, Dong YB, Zhang K, Li B, Zhao WD, Fang WG, Chen YH (2016) Intracerebral GM-CSF contributes to transendothelial monocyte migration in APP/PS1 Alzheimer’s disease mice. J Cereb Blood Flow Metab 36(11):1978–1991

    CAS  PubMed  PubMed Central  Google Scholar 

  55. Jang JC, Li J, Gambini L, Batugedara HM, Sati S, Lazar MA, Fan L, Pellecchia M, Nair MG (2017) Human resistin protects against endotoxic shock by blocking LPS-TLR4 interaction. Proc Natl Acad Sci USA 114(48):E10399–E10408

    CAS  PubMed  PubMed Central  Google Scholar 

  56. Verma S, Li SH, Wang CH, Fedak PW, Li RK, Weisel RD, Mickle DA (2003) Resistin promotes endothelial cell activation: further evidence of adipokine-endothelial interaction. Circulation 108(6):736–740

    CAS  PubMed  Google Scholar 

  57. Kougias P, Chai H, Lin PH, Yao Q, Lumsden AB, Chen C (2005) Effects of adipocyte-derived cytokines on endothelial functions: implication of vascular disease. J Surg Res 126(1):121–129

    CAS  PubMed  Google Scholar 

  58. Calabro P, Samudio I, Willerson JT, Yeh ET (2004) Resistin promotes smooth muscle cell proliferation through activation of extracellular signal-regulated kinase 1/2 and phosphatidylinositol 3-kinase pathways. Circulation 110(21):3335–3340

    CAS  PubMed  Google Scholar 

  59. Tarkowski A, Bjersing J, Shestakov A, Bokarewa MI (2010) Resistin competes with lipopolysaccharide for binding to toll-like receptor 4. J Cell Mol Med 14(6B):1419–1431

    CAS  PubMed  Google Scholar 

  60. Middeldorp J, Hol EM (2011) GFAP in health and disease. Prog Neurobiol 93(3):421–443

    CAS  PubMed  Google Scholar 

  61. Pekny M, Nilsson M (2005) Astrocyte activation and reactive gliosis. Glia 50(4):427–434

    PubMed  Google Scholar 

  62. Liedtke W, Edelmann W, Chiu FC, Kucherlapati R, Raine CS (1998) Experimental autoimmune encephalomyelitis in mice lacking glial fibrillary acidic protein is characterized by a more severe clinical course and an infiltrative central nervous system lesion. Am J Pathol 152(1):251–259

    CAS  PubMed  PubMed Central  Google Scholar 

  63. Li L, Lundkvist A, Andersson D, Wilhelmsson U, Nagai N, Pardo AC, Nodin C, Ståhlberg A, Aprico K, Larsson K, Yabe T, Moons L, Fotheringham A, Davies I, Carmeliet P, Schwartz JP, Pekna M, Kubista M, Blomstrand F, Maragakis N, Nilsson M, Pekny M (2008) Protective role of reactive astrocytes in brain ischemia. J Cereb Blood Flow Metab 28(3):468–481

    PubMed  Google Scholar 

  64. Liu Z, Li Y, Cui Y, Roberts C, Lu M, Wilhelmsson U, Pekny M, Chopp M (2014) Beneficial effects of gfap/vimentin reactive astrocytes for axonal remodeling and motor behavioral recovery in mice after stroke. Glia 62(12):2022–2033

    PubMed  PubMed Central  Google Scholar 

  65. Macauley SL, Pekny M, Sands MS (2011) The role of attenuated astrocyte activation in infantile neuronal ceroid lipofuscinosis. J Neurosci 31(43):15575–15585

    CAS  PubMed  PubMed Central  Google Scholar 

  66. Kraft AW, Hu X, Yoon H, Yan P, Xiao Q, Wang Y, Gil SC, Brown J, Wilhelmsson U, Restivo JL, Cirrito JR, Holtzman DM, Kim J, Pekny M, Lee JM (2013) Attenuating astrocyte activation accelerates plaque pathogenesis in APP/PS1 mice. FASEB J 27(1):187–198

    CAS  PubMed  PubMed Central  Google Scholar 

  67. Jiang Y, Lu L, Hu Y, Li Q, An C, Yu X, Shu L, Chen A, Niu C, Zhou L, Yang Z (2016) Resistin induces hypertension and insulin resistance in mice via a TLR4-dependent pathway. Sci Rep 6:22193

    CAS  PubMed  PubMed Central  Google Scholar 

  68. Zamora C, Cantó E, Nieto JC, Angels Ortiz M, Juarez C, Vidal S (2012) Functional consequences of CD36 downregulation by TLR signals. Cytokine 60(1):257–265

    CAS  PubMed  Google Scholar 

  69. Sansing LH, Harris TH, Welsh FA, Kasner SE, Hunter CA, Kariko K (2011) Toll-like receptor 4 contributes to poor outcome after intracerebral hemorrhage. Ann Neurol 70(4):646–656

    CAS  PubMed  PubMed Central  Google Scholar 

  70. Lee S, Lee HC, Kwon YW, Lee SE, Cho Y, Kim J, Lee S, Kim JY, Lee J, Yang HM, Mook-Jung I, Nam KY, Chung J, Lazar MA, Kim HS (2014) Adenylyl cyclase-associated protein 1 is a receptor for human resistin and mediates inflammatory actions of human monocytes. Cell Metab 19(3):484–497

    CAS  PubMed  PubMed Central  Google Scholar 

  71. Onuma H, Tabara Y, Kawamura R, Ohashi J, Nishida W, Takata Y, Ochi M, Nishimiya T, Kawamoto R, Kohara K, Miki T, Osawa H (2013) Plasma resistin is associated with single nucleotide polymorphisms of a possible resistin receptor, the decorin gene, in the general Japanese population. Diabetes 62(2):649–652

    CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

This research was supported by grants from the National Natural Science Foundation of China (Grant Nos. 30600327, 31571057), Liaoning Provincial Department of Education Key Laboratory project (Grant No. LZ2015074), Shenyang Science and Technology Plan Project (Grant Nos. 17-230-9-31 and F16-206-9-03).

Author information

Authors and Affiliations

  1. Department of Developmental Cell Biology, Key Laboratory of Cell Biology, Key Laboratory of Medical Cell Biology, Ministry of Education, Ministry of Public Health, China Medical University, No. 77 Puhe Road, Shenyang North New Area, Shenyang, Liaoning, People’s Republic of China

    Liu Xiaoying, Tian Li, Shang Yu, Jiang Jiusheng, Zhang Jilin, Wei Jiayi, Liu Dongxin, Fang Wengang, Chen Yuhua & Shang Deshu

  2. Deparment of Geriatrics, Shengjing Hospital of China Medical University, No. 36 Sanhao Street, Heping District, Shenyang, Liaoning, People’s Republic of China

    Tian Li

  3. Class 81, Phase 102, China Medical University, No. 77 Puhe Road, Shenyang North New Area, Shenyang, Liaoning, People’s Republic of China

    Zhao Xinyue & Yu Hao

  4. Department of Developmental Cell Biology, Cell Biology Division, Key Laboratory of Cell Biology, Key Laboratory of Medical Cell Biology, Ministry of Education, Ministry of Public Health, China Medical University, 110122, Shenyang, Liaoning, People’s Republic of China

    Chen Yuhua & Shang Deshu

Authors
  1. Liu Xiaoying
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Tian Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Shang Yu
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Jiang Jiusheng
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Zhang Jilin
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Wei Jiayi
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Liu Dongxin
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Fang Wengang
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Zhao Xinyue
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Yu Hao
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Chen Yuhua
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Shang Deshu
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Chen Yuhua or Shang Deshu.

Additional information

Publisher’s Note

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

Electronic supplementary material

Below is the link to the electronic supplementary material.

11064_2019_2726_MOESM1_ESM.tif

Supplemental figure 1. Resistin-treated NSCs proliferation in vitro. (A) NSCs were seeded in 96-well plates, resistin at 10 and 100 ng/ml were incubated with NSCs for 12 hours, 24 hours, 36 hours, and 72 hours. Then, 10 μl of CCK8 solution was added to each well and incubated for 4 hours. The OD was measured in a spectrophotometer at 450 nm wavelength. p>0.05 vs. control. (B) Cell cycle of resistin-treated NSCs. NSCs were treated with 10 and 100 ng/ml resistin for 24 hours and 72 hours, and the cell cycle was measured by flow cytometry. (C) Statistical analysis of cell cycle. p>0.05 vs. corresponding controls at different time points. All the experiments were independently performed three times (n=3)—Supplementary material 1 (TIF 10195 KB)

11064_2019_2726_MOESM2_ESM.tif

Supplemental figure 2. Effects of resistin on NSC differentiation markers expression under unidirectional culture system. (A) Analysis of immunofluorescence staining. Adherently growing neural stem cells exposed to 10 ng/ml or 100 ng/ml resistin for 7 days in unidirectional differentiation medium. GFAP expression was visualized by immunofluorescence (red) and Nestin expression was visualized by FITC (green). DAPI was used to visualize cell nuclei (blue). Scale bar: 100 μm. (B) Western blot analysis of NSCs differentiation markers GFAP, nestin and PCNA expression. Statistical analysis of nestin (C), GFAP (D) and PCNA (E). One-way ANOVA was used for repeated measurements, n=3, *p<0.05 or **p<0.01 vs. control—Supplementary material 2 (TIF 19634 KB)

11064_2019_2726_MOESM3_ESM.tif

Supplemental figure 3. Resistin-induced CD36 Gene and protein expression changes in directed astrocyte differentiation from NSCs. Adherently growing neural stem cells exposed to 10 ng/ml or 100 ng/ml resistin for 7 days in directional differentiation medium. The results of real-time PCR (A) and Western blot (B) show CD36 mRNA and protein levels expression, respectively. One-way ANOVA was used for repeated measurements, n=3, Data are shown as the means ± standard deviations (SD). *p<0.05 or **p<0.01 vs. control—Supplementary material 3 (TIF 4427 KB)

11064_2019_2726_MOESM4_ESM.tif

Supplemental figure 4. Efficiency of transfection. Adherently growing neural stem cells were transfected with 5-carboxy-fluorescein (FAM)-labelled siTLR4 for 24 h. Bright field (A) or fluorescence microscopy (B) shows the efficiency of transfection—Supplementary material 4 (TIF 3115 KB)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Xiaoying, L., Li, T., Yu, S. et al. Resistin-Inhibited Neural Stem Cell-Derived Astrocyte Differentiation Contributes to Permeability Destruction of the Blood–Brain Barrier. Neurochem Res 44, 905–916 (2019). https://doi.org/10.1007/s11064-019-02726-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11064-019-02726-3

Keywords

Search

Navigation