Advertisement

Journal of Molecular Histology

, Volume 43, Issue 5, pp 543–552 | Cite as

The cell-specific upregulation of bone morphogenetic protein-10 (BMP-10) in a model of rat cortical brain injury

  • Yaohua Yan
  • Peipei Gong
  • Wei Jin
  • Jian Xu
  • Xiaohong Wu
  • Ting Xu
  • Qinglei Hang
  • Hongran Fu
  • Kaifu Kei
  • Yilu Gao
Original Paper

Abstract

Previous studies have suggested that bone morphogenetic protein-6 (BMP-6) has a pronounced upregulation in rat brains subjected to traumatic brain injury. Bone morphogenetic protein-10 (BMP-10) is a newly identified cardiac-specific peptide growth factor that belongs to the TGF-β superfamily. To elucidate the dynamic expression changes and cellular localization of BMP-10 during traumatic brain injury (TBI), we performed an acute traumatic brain injury model in adult rats. Western blot analysis, immunohistochemistry and RTPCR revealed that BMP-10 expression in impaired cerebral cortex was more strongly induced not only at protein level but also at mRNA level compared to that in normal group. Double immunofluorescence labeling suggested that BMP-10 was localized mainly in the cytoplasm of neurons, microglias, and astrocytes within 3 mm from the lesion site at day 3 post-injury. And there was a specific upregulation of BMP-10 in astrocytes following brain injury. Besides, co-localization of BMP-10 and proliferating cell nuclear antigen (PCNA) was detected in Glial fibrillary acidic protein (GFAP) + cells. We also examined the expression profiles of PCNA and GFAP whose change was correlated with the expression profiles of BMP-10 in the incised injury model used here. Another experiment in which astrocytes were treated with BMP-10 was also performed to confirm the relationship between the upregulation of BMP-10 and proliferation of astrocytes following TBI. Taken together, this is the first description of BMP-10 expression during the central nervous system (CNS) lesion and repair. Thus, the present data suggested that BMP-10 may be implicated in CNS pathophysiology after TBI. But, further studies are needed to understand the cell signal pathway which can direct the exact role of BMP-10 following traumatic brain injury.

Keywords

BMP-10 Traumatic brain injury Proliferation Astrocytes Rat 

Notes

Acknowledgments

This study was supported by the National Natural Science Foundation of China (No. 81070992) and A Project Funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD).

References

  1. Beckham JD, Tuttle K, Tyler KL (2009) Reovirus activates transforming growth factor beta and bone morphogenetic protein signaling pathways in the central nervous system that contribute to neuronal survival following infection. J Virol 83:5035–5045PubMedCrossRefGoogle Scholar
  2. Chen Y, Swanson RA (2003) Astrocytes and brain injury. J Cereb Blood Flow Metab 23:137–149PubMedCrossRefGoogle Scholar
  3. Chen XH, Iwata A, Nonaka M et al (2003) Neurogenesis and glial proliferation persist for at least one year in the subventricular zone following brain trauma in rats. J Neurotrauma 20:623–631PubMedCrossRefGoogle Scholar
  4. Chen H, Shi S, Acosta L et al (2004) BMP-10 is essential for maintaining cardiac growth during murine cardiogenesis. Development 131:2219–2231PubMedCrossRefGoogle Scholar
  5. Colak D, Mori T, Brill MS et al (2008) Adult neurogenesis requires Smad4-mediated bone morphogenic protein signaling in stem cells. J Neurosci 28:434–446PubMedCrossRefGoogle Scholar
  6. David L, Mallet C, Mazerbourg S et al (2007) Identification of BMP9 and BMP-10 as functional activators of the orphan activin receptor-like kinase 1 (ALK1) in endothelial cells. Blood 109:1953–1961PubMedCrossRefGoogle Scholar
  7. Di Giovanni S, Movsesyan V, Ahmed F et al (2005) Cell cycle inhibition provides neuroprotection and reduces glial proliferation and scar formation after traumatic brain injury. Proc Natl Acad Sci USA 102:8333–8338PubMedCrossRefGoogle Scholar
  8. Dijke Pt (2006) Bone morphogenetic protein signal transduction in bone. Curr Med Res Opin 1:S7–S11CrossRefGoogle Scholar
  9. Fernández-L A, Sanz-Rodriguez F, Blanco FJ et al (2006) Hereditary hemorrhagic telangiectasia, a vascular dysplasia affecting the TGF-beta signaling pathway. Clin Med Res 4:66–78PubMedCrossRefGoogle Scholar
  10. Galter D, Böttner M, Krieglstein K et al (1999) Differential regulation of distinct phenotypic features of serotonergic neurons by bone morphogenetic proteins. Eur J Neurosci 1:2444–2452CrossRefGoogle Scholar
  11. Goto K, Tong KI, IKura J et al (2011) HLA-B-associated transcript 3 (Bat3/Scythe) negatively regulates Smad phosphorylation in BMP signaling. Cell Death Dis 2:e236PubMedCrossRefGoogle Scholar
  12. Hall AK, Miller RH (2004) Emerging roles for bone morphogenetic proteins in central nervous system glial biology. J Neurosci Res 76:1–8PubMedCrossRefGoogle Scholar
  13. Hampton DW, Asher RA, Kondo T et al (2007) A potential role for bone morphogenetic protein signalling in glial cell fate determination following adult central nervous system injury in vivo. Eur J Neurosci 26:3024–3035PubMedCrossRefGoogle Scholar
  14. Heegaard W, Biros M (2007) Traumatic brain injury. Emerg Med Clin North Am 25:655–678PubMedCrossRefGoogle Scholar
  15. Herrmann JE, Imura T, Song B et al (2008) STAT3 is a critical regulator of astrogliosis and scar formation after spinal cord injury. J Neurosci 28:7231–7243PubMedCrossRefGoogle Scholar
  16. Israelsson C, Bengtsson H, Kylberg A et al (2008) Distinct cellular patterns of upregulated chemokine expression supporting a prominent inflammatory role in traumatic brain injury. J Neurotrauma 25:959–974PubMedCrossRefGoogle Scholar
  17. Keane RW, Kraydieh S, Lotocki G et al (2001) Apoptotic and antiapoptotic mechanisms after traumatic brain injury. J Cereb Blood Flow Metab 21:1189–1198PubMedCrossRefGoogle Scholar
  18. Knoblach SM, Faden AI (1998) Interleukin-10 improves outcome and alters proinflammatory cytokine expression after experimental traumatic brain injury. Exp Neurol 153:143–151PubMedCrossRefGoogle Scholar
  19. Langlois JA, Rutland-Brown W, Wald MM (2006) The epidemiology and impact of traumatic brain injury: a brief overview. J Head Trauma Rehabil 21:375–378PubMedCrossRefGoogle Scholar
  20. Liu Y, Wang Y, Cheng C et al (2010) A relationship between p27(kip1) and Skp2 after adult brain injury: implications for glial proliferation. J Neurotrauma 27:361–371PubMedCrossRefGoogle Scholar
  21. Lloyd E, Somera-Molina K, Van Eldik LJ et al (2008) Suppression of acute proinflammatory cytokine and chemokine upregulation by post-injury administration of a novel small molecule improves long-term neurologic outcome in a mouse model of traumatic brain injury. J Neuroinflammation 5:28PubMedCrossRefGoogle Scholar
  22. Mazerbourg S, Sangkuhl K, Luo CW et al (2005) Identification of receptors and signaling pathways for orphan bone morphogenetic protein/growth differentiation factor ligands based on genomic analyses. J Biol Chem 280:32122–32132PubMedCrossRefGoogle Scholar
  23. McKee JA, Brewer RP, Macy GE et al (2005) Magnesium neuroprotection is limited in humans with acute brain injury. Neurocrit Care 2:342–351PubMedCrossRefGoogle Scholar
  24. Myer DJ, Gurkoff GG, Lee SM et al (2006) Essential protective roles of reactive astrocytes in traumatic brain injury. Brain 129:2761–2772PubMedCrossRefGoogle Scholar
  25. Neuhaus H, Rosen V, Thies RS (1999) Heart specific expression of mouse BMP-10 a novel member of the TGF-b superfamily. Mech Dev 80:181–184PubMedCrossRefGoogle Scholar
  26. Setoguchi T, Yone K, Matsuoka E et al (2001) Traumatic injury induced BMP7 expression in the adult rat spinal cord. Brain Res 921:219–225PubMedCrossRefGoogle Scholar
  27. Shi Y, Massagué J (2003) Mechanisms of TGF-beta signaling from cell membrane to the nucleus. Cell 113:685–700PubMedCrossRefGoogle Scholar
  28. Silver J, Miller JH (2004) Regeneration beyond the glial scar. Nat Rev Neurosci 5:146–156PubMedCrossRefGoogle Scholar
  29. Sofroniew MV (2009) Molecular dissection of reactive astrogliosis and glial scar formation. Trends Neurosci 32:638–647PubMedCrossRefGoogle Scholar
  30. Sofroniew MV, Vinters HV (2010) Astrocytes: biology and pathology. Acta Neuropathol 119:7–35PubMedCrossRefGoogle Scholar
  31. Suzuki Y, Ohga N, Morishita Y et al (2010) BMP-9 induces proliferation of multiple types of endothelial cells in vitro and in vivo. J Cell Sci 123:1684–1692PubMedCrossRefGoogle Scholar
  32. Teichmann U, Kessel M (2003) Highly restricted BMP10 expression in the trabeculating myocardium of the chick embryo. Dev Genes Evol 214:96–98CrossRefGoogle Scholar
  33. Wozney JM (1998) The bone morphogenetic protein family: multifunctional cellular regulators in the embryo and adult. Eur J Oral Sci 1:160–166Google Scholar
  34. Xiao Q, Du Y, Wu W et al (2010) Bone morphogenetic proteins mediate cellular response and, together with Noggin, regulate astrocyte differentiation after spinal cord injury. Exp Neurol 221:353–366PubMedCrossRefGoogle Scholar
  35. Ye L, Kynaston H, Jiang WG (2009) Bone morphogenetic protein-10 suppresses the growth and aggressiveness of prostate cancer cells through a Smad independent pathway. J Urol 181:2749–2759PubMedCrossRefGoogle Scholar
  36. Ye L, Bokobza S, Li J et al (2010) Bone morphogenetic protein-10 (BMP-10) inhibits aggressiveness of breast cancer cells and correlates with poor prognosis in breast cancer. Cancer Sci 101:2137–2144PubMedCrossRefGoogle Scholar
  37. Zhang Z, Trautmann K, Artelt M et al (2006) Bone morphogenetic protein-6 is expressed early by activated astrocytes in lesions of rat traumatic brain injury. Neuroscience 138:47–53PubMedCrossRefGoogle Scholar
  38. Zweckberger K, Eros C, Zimmermann R et al (2006) Effect of early and delayed decompressive craniectomy on secondary brain damage after controlled cortical impact in mice. J Neurotrauma 23:1083–1093PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media B.V. 2012

Authors and Affiliations

  • Yaohua Yan
    • 1
  • Peipei Gong
    • 1
  • Wei Jin
    • 2
  • Jian Xu
    • 1
  • Xiaohong Wu
    • 2
  • Ting Xu
    • 1
  • Qinglei Hang
    • 1
  • Hongran Fu
    • 2
  • Kaifu Kei
    • 2
  • Yilu Gao
    • 1
  1. 1.Department of NeurosurgeryAffiliated Hospital of Nantong UniversityNantongPeople’s Republic of China
  2. 2.Department of NeurologyAffiliated Hospital of Nantong UniversityNantongPeople’s Republic of China

Personalised recommendations