Cellular and Molecular Neurobiology

, Volume 36, Issue 6, pp 1001–1013 | Cite as

T-cell factor (TCF/LEF1) binding elements (TBEs) of FasL (Fas ligand or CD95 ligand) bind and cluster Fas (CD95) and form complexes with the TCF-4 and b-catenin transcription factors in vitro and in vivo which result in triggering cell death and/or cell activation

  • Xia Liu
  • Yuwei Huang
  • Yuanyuan Zhang
  • Xiaohong Li
  • Chun Liu
  • Shen Huang
  • Dezhi Xu
  • Yang WuEmail author
  • Xiaojuan LiuEmail author
Original Research


T-cell factor 4 (TCF4) is an important transcription factor of the Wnt signaling system. β-catenin, an upstream protein of TCF4, accumulates in the cytoplasm, then translocates to the nucleus to activate the β-catenin/T-cell factor/lymphoid enhancer factor (TCF/LEF) transcriptional machinery and regulates target genes. Previous studies showed that TCF4 was involved in cell proliferation and apoptosis. However, its expression and function in central nervous system injury are unclear. We performed a traumatic brain injury (TBI) model in adult rats. The expression of TCF4 in the brain cortex detected by Western blot increased after TBI. Double immunofluorescence staining revealed that TCF4 was expressed by neurons and microglia. In addition, co-localization of TCF4 with active caspase-3 or proliferating cell nuclear antigen was observed in neurons and microglia, respectively, suggesting that TCF4 might participate in neuronal apoptosis and microglial proliferation after TBI. To further investigate the functions of TCF4, PC12 and HAPI cells were employed to establish a neuronal apoptosis and microglial proliferation model in vitro, respectively. Knocking down TCF4 with siRNA proved the pro-apoptotic and pro-proliferation effect of TCF4 in PC12 and HAPI cells, respectively. Taken together, TCF4 might promote neuronal apoptosis and microglial proliferation after TBI.


Traumatic brain injury Rat T-cell factor 4 (TCF4) Apoptosis Proliferation Cell cycle protein 



This work was supported in part by the National Natural Science Foundation of China (nos. 81401365, 81373223, 81200918, 81172879, 30770666, 30973143, 31201083), a project funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD).

Compliance with Ethical Standards

Conflict of Interests

All authors declare that they have no conflict of interest.


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Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  • Xia Liu
    • 1
    • 9
  • Yuwei Huang
    • 2
    • 9
  • Yuanyuan Zhang
    • 3
  • Xiaohong Li
    • 4
    • 9
  • Chun Liu
    • 5
    • 8
  • Shen Huang
    • 6
    • 9
  • Dezhi Xu
    • 7
    • 9
  • Yang Wu
    • 2
    Email author
  • Xiaojuan Liu
    • 8
    • 9
    Email author
  1. 1.Department of Pathophysiology, Medical CollegeNantong UniversityNantongPeople’s Republic of China
  2. 2.Institute of Nautical MedicineNantong UniversityNantongPeople’s Republic of China
  3. 3.Affiliated Hospital of Nantong UniversityNantongPeople’s Republic of China
  4. 4.Surgical Comprehensive LaboratoryAffiliated Hospital of Nantong UniversityNantongPeople’s Republic of China
  5. 5.Laboratory Animal CenterNantong UniversityNantongPeople’s Republic of China
  6. 6.Department of Osteology, The Second Affiliated HospitalNantong UniversityNantongPeople’s Republic of China
  7. 7.Department of NeurosurgeryWuxi Second Hospital Affiliated to Nanjing Medical UniversityWuxiPeople’s Republic of China
  8. 8.Department of Pathogen Biology, Medical CollegeNantong UniversityNantongPeople’s Republic of China
  9. 9.Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Medical CollegeNantong UniversityNantongPeople’s Republic of China

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