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Changes in the BAG1 Expression of Schwann Cells After Sciatic Nerve Crush

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Abstract

Bcl-2-associated athanogene-1 (BAG1), a co-chaperone for Hsp70/Hsc70, is a multifunctional protein, which has been shown to suppress apoptosis and enhance neuronal differentiation. However, the expression and roles of BAG1 in peripheral system lesions and repair are still unknown. In this study, we investigated the dynamic changes in BAG1 expression in an acute sciatic nerve crush model in adult rats. Western blot analysis revealed that BAG1 was expressed in normal sciatic nerves. BAG1 expression increased progressively after sciatic nerve crush, reached a peak 2 weeks post-injury, and then returned to the normal level 4 weeks post-injury. Spatially, we observed that BAG1 was mainly expressed in Schwann cells and that BAG1 expression increased in Schwann cells after injury. In vitro, we found that BAG1 expression increased during the cyclic adenosine monophosphate (cAMP)-induced Schwann cell differentiation process. BAG1-specific siRNA inhibited cAMP-induced Schwann cell differentiation. In conclusion, we speculated that BAG1 was upregulated in the sciatic nerve after crush, which was associated with Schwann cell differentiation.

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Abbreviations

BAG1:

Bcl-2-associated athanogene-1

SCs:

Schwann cells

GAPDH:

Glyceraldehyde-3-phosphate dehydrogenase

PNS:

Peripheral nervous system

CNS:

Central nerve system

SNC:

Sciatic nerve crush

cAMP:

Cyclic adenosine monophosphate

References

  • Arroyo EJ, Bermingham JR Jr, Rosenfeld MG, Scherer SS (1998) Promyelinating Schwann cells express Tst-1/SCIP/Oct-6. J Neurosci 18(19):7891–7902

    Google Scholar 

  • Brockes JP, Fields KL, Raff MC (1979) Studies on cultured rat Schwann cells. I. Establishment of purified populations from cultures of peripheral nerve. Brain Res 165(1):105–118

    Google Scholar 

  • Chen ZL, Yu WM, Strickland S (2007) Peripheral regeneration. Annu Rev Neurosci 30:209–233

    Article  PubMed  Google Scholar 

  • Cheng C, Qin Y, Shao X, Wang H, Gao Y, Cheng M, Shen A (2007) Induction of TNF-alpha by LPS in Schwann cell is regulated by MAPK activation signals. Cell Mol Neurobiol 27(7):909–921

    Article  PubMed  CAS  Google Scholar 

  • Fawcett JW, Keynes RJ (1990) Peripheral nerve regeneration. Annu Rev Neurosci 13:43–60

    Article  PubMed  CAS  Google Scholar 

  • Fu SY, Gordon T (1997) The cellular and molecular basis of peripheral nerve regeneration. Mol Neurobiol 14(1–2):67–116

    Article  PubMed  CAS  Google Scholar 

  • Goldberg JL, Barres BA (2000) The relationship between neuronal survival and regeneration. Annu Rev Neurosci 23:579–612

    Article  PubMed  CAS  Google Scholar 

  • Gotz R, Wiese S, Takayama S, Camarero GC, Rossoll W, Schweizer U et al (2005) Bag1 is essential for differentiation and survival of hematopoietic and neuronal cells. Nat Neurosci 8(9):1169–1178

    Article  PubMed  Google Scholar 

  • Hall SM (1986) The effect of inhibiting Schwann cell mitosis on the reinnervation of acellular autografts in the peripheral nervous system of the mouse. Neuropathol Appl Neurobiol 12:401–414

    Article  PubMed  CAS  Google Scholar 

  • Huang YL, Ding M, Hansson HA (1998) Dorsal root ganglion nerve cells transiently express increased immunoreactivity of the calcium-binding protein S-100beta after sciatic nerve transection. Brain Res 785(2):351–354

    Article  PubMed  CAS  Google Scholar 

  • Jessen KR, Mirsky R (1999) Schwann cells and their precursors emerge as major regulators of nerve development. Trends Neurosci 22(9):402–410

    Article  PubMed  CAS  Google Scholar 

  • Ji Y, Tao T, Cheng C, Yang H, Wang Y, Yang J, Liu H, He X, Wang H, Shen A (2010) SSeCKS is a suppressor in Schwann cell differentiation and myelination. Neurochem Res 35(2):219–226

    Google Scholar 

  • Kermer P, Krajewska M, Zapata JM, Takayama S, Mai J, Krajewski S et al (2002) Bag1 is a regulator and marker of neuronal differentiation. Cell Death Differ 9:405–413

    Article  PubMed  CAS  Google Scholar 

  • Kermer P, Digicaylioglu MH, Kaul M, Zapata JM, Krajewska M, Stenner-Liewen F et al (2003) BAG1 over-expression in brain protects against stroke. Brain Pathol 13(9):495–506

    PubMed  CAS  Google Scholar 

  • Kioussi C, Gruss P (1996) Making of a Schwann. Trends Genet 12(3):84–86

    Article  PubMed  CAS  Google Scholar 

  • Lee SK, Wolfe SW (2000) Peripheral nerve injury and repair. J Am Acad OrthopSurg 8(4):243–252

    CAS  Google Scholar 

  • Lemke G, Chao M (1988) Axons regulate Schwann cell expression of the major myelin and NGF receptor genes. Development 102(3):499–504

    PubMed  CAS  Google Scholar 

  • Liu HM, Yang LH, Yang YJ (1995) Schwann cell properties: C-fos expression, bFGF production, phagocytosis and proliferation during Wallerian degeneration. J Neuropathol Exp Neurol 54(4):487–496

    Article  PubMed  CAS  Google Scholar 

  • Lou D, Sun B, Wei H, Deng X, Chen H, Xu D, Li G, Xu H, Wang Y (2012) Spatiotemporal expression of testicular protein kinase 1 after rat sciatic nerve injury. J Mol Neurosci 47(1):180–191

    Article  PubMed  CAS  Google Scholar 

  • Lundborg G (2003) Bunge memorial lecture. Nerve injury and repair—a challenge to the plastic brain. J Peripher Nerv Syst 8(4):209–226

    Article  PubMed  Google Scholar 

  • Mathon NF, Malcolm DS, Harrisingh MC, Cheng L, Lloyd AC (2001) Lack of replicative senescence in normal rodent glia. Science 291 (5505):872–875

    Google Scholar 

  • Michailov GV, Sereda MW, Brinkmann BG, Fischer TM, Haug B, Birchmeier C, Role L, Lai C, Schwab MH, Nave KA (2004) Axonal neuregulin-1 regulates myelin sheath thickness. Science 304(5671):700–703

    Article  PubMed  CAS  Google Scholar 

  • Morgan L, Jessen KR, Mirsky R (1991) The effects of cAMP on differentiation of cultured Schwann cells: progression from an early phenotype (04+) to a myelin phenotype (P0+, GFAP−, N−CAM−, NGF− receptor−) depends on growth inhibition. J Cell Biol 112(3):457–467

    Article  PubMed  CAS  Google Scholar 

  • Murinson BB, Archer DR, Li Y, Griffin JW (2005) Degeneration of myelinated efferent fibers prompts mitosis in Remak Schwann cells of uninjured C-fiber afferents. J Neurosci 25(5):1179–1187

    Article  PubMed  CAS  Google Scholar 

  • Pellegrino RG, Politis MJ, Ritchie JM, Spencer PS (1986) Events in degenerating cat peripheral nerve: induction of Schwann cell S phase and its relation to nerve fibre degeneration. J Neurocytol 15(1):17–28

    Article  PubMed  CAS  Google Scholar 

  • Planchamp V, Bermel C, Tonges L, Ostendorf T et al (2008) BAG1 promotes axonal outgrowth and regeneration in vivo via Raf-1 and reduction of ROCK activity. Brain 131(10):2606–2619

    Article  PubMed  Google Scholar 

  • Rotshenker S (2011) Wallerian degeneration: the innate-immune response to traumatic nerve injury. J Neuroinflammation 8:109

    Article  PubMed  CAS  Google Scholar 

  • Takayama S, Sato T, Krajewski S, Kochel K, Irie S, Millan JA et al (1995) Cloning and functional analysis of BAG-1: a novel Bcl-2-binding protein with anti-cell death activity. Cell 80(2):279–284

    Article  PubMed  CAS  Google Scholar 

  • Takayama S, Xie Z, Reed JC (1999) An evolutionarily conserved family of Hsp70/Hsc70 molecular chaperone regulators. J Biol Chem 274(2):781–786

    Article  PubMed  CAS  Google Scholar 

  • Tao T, Ji Y, Chen C, Yang H, Liu H, Sun L, Qin Y, Yang J, Wang H, Shen A (2009) Tumor necrosis factor-alpha inhibits Schwann cell proliferation by up-regulating Src-suppressed protein kinase C substrate expression. J Neurochem 111(3):647–655

    Article  PubMed  CAS  Google Scholar 

  • Taveggia C, Zanazzi G, Petrylak A, Yano H, Rosenbluth J, Einheber S, Xu X, Esper RM, Loeb JA, Shrager P, Chao MV, Falls DL, Role L, Salzer JL (2005) Neuregulin-1 type III determines the ensheathment fate of axons. Neuron 47(5):681–694

    Article  PubMed  CAS  Google Scholar 

  • Trapp BD, Hauer P, Lemke G (1988) Axonal regulation of myelin protein mRNA levels in actively myelinating Schwann cells. J Neurosci 8(9):3515–3521

    PubMed  CAS  Google Scholar 

  • Vargas ME, Barres BA (2007) Why is Wallerian degeneration in the CNS so slow? Annu Rev Neurosci 30:153–179

    Article  PubMed  CAS  Google Scholar 

  • Wang Q, Wang Y, Zhou Z, Lu X, Cao Y, Liu Y, Yan M, He F, Pan X, Qian X, Ji Y, Yang H (2011) Expressions of forkhead class box O 3a on crushed rat sciatic nerves and differentiated primary Schwann cells. Cell Mol Neurobiol 31(4):509–518

    Article  PubMed  CAS  Google Scholar 

  • White FV, Toews AD, Goodrum JF, Novicki DL, Bouldin TW, Morell P (1989) Lipid metabolism during early stages of Wallerian degeneration in the rat sciatic nerve. J Neurochem 52(4):1085–1092

    Article  PubMed  CAS  Google Scholar 

  • Yang DP, Zhang DP, Mak KS, Bonder DE, Pomeroy SL, Kim HA (2008) Schwann cell proliferation during Wallerian degeneration is not necessary for regeneration and remyelination of the peripheral nerves: axon-dependent removal of newly generated Schwann cells by apoptosis. Mol Cell Neurosci 38(1):80–88

    Article  PubMed  CAS  Google Scholar 

  • Yang J, Cao J, et al (2012) Transcription initiation factor IIB involves in Schwann cell differentiation after rat sciatic nerve crush. J Mol Neurosci. doi:10.1007/s12031-012-9865-7

  • Zeiner M, Gehring U (1995) A protein that interacts with members of the nuclear hormone receptor family: identification and cDNA cloning. Proc Natl Acad Sci USA 92(25):11465–11469

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This work was supported by the National Natural Science Foundation of China (no. 81171140, no. 30300099, no. 30770488, and no. 30870320), Natural Science Foundation of Jiangsu Province (no. BK2009161, no. BK2009156, and no. BK2009157), Natural Science Foundation of Jiangsu Colleges and Universities Grant (09KJD310005), and the Society and Technology Grew Project of Nantong City (S2008020).

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Authors and Affiliations

  1. Department of Orthopaedics, Affiliated Hospital of Nantong University, Nantong University, Nantong, 226001, Jiangsu, People’s Republic of China

    Hao Wu, Long Long, Xinghai Cheng, Hai Weng, Tao Ding, Haixiang Wei, Ming Li, Weipeng Huan, Xiaolong Deng & Youhua Wang

  2. Department of Pathogen Biology, Medical College, Nantong University, Nantong, 226001, Jiangsu, People’s Republic of China

    Yonghua Liu

  3. Department of Anesthesiology, Affiliated Hospital of Nantong University, Nantong University, Nantong, 226001, Jiangsu, People’s Republic of China

    Yuan Zhou

  4. Department of Gynecology & Obstetrics, Chengnan Hospital, Yancheng, 224005, Jiangsu, People’s Republic of China

    Lei Ji

  5. Department of Immunology, Medical College, Nantong University, 19 Qi-Xiu Road, Nantong, Jiangsu Province, 226001, People’s Republic of China

    Jiao Yang

Authors
  1. Hao Wu
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  2. Yonghua Liu
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  3. Yuan Zhou
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  4. Long Long
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  5. Xinghai Cheng
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  9. Jiao Yang
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  10. Haixiang Wei
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  11. Ming Li
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  12. Weipeng Huan
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  13. Xiaolong Deng
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  14. Youhua Wang
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Corresponding author

Correspondence to Youhua Wang.

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Hao Wu and Yonghua Liu contributed equally to this work.

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Wu, H., Liu, Y., Zhou, Y. et al. Changes in the BAG1 Expression of Schwann Cells After Sciatic Nerve Crush. J Mol Neurosci 49, 512–522 (2013). https://doi.org/10.1007/s12031-012-9910-6

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  • DOI: https://doi.org/10.1007/s12031-012-9910-6

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