Journal
CNS NEUROSCIENCE & THERAPEUTICS
Volume 26, Issue 9, Pages 940-951Publisher
WILEY
DOI: 10.1111/cns.13390
Keywords
glial scar; reprogramming; spinal cord injury; transcription factor
Categories
Funding
- National Natural Science Foundation of China [81772379, 81572177, 81972096]
- Scientific Research Fund of Zhejiang Provincial Education Department [Y201941476]
- Health Foundation of Zhejiang Province [2018241121]
- Natural Science Foundation of Zhejiang Province [LY18H060004]
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Introduction Astrogliosis and glial scar formation following spinal cord injury (SCI) are viewed as major obstacles that hinder axonal regeneration and functional recovery. Regulating the glial scar and axonal regeneration in the lesion site is important for treating SCI. Aims Considering the important role of astrocyte in glial scar formation and subsequent axonal regeneration, we intended to investigate the effect of the transcription factors OCT4 and KLF4 on astrocyte and the underlying mechanism after spinal cord contusion injury in transgenic mice. Results Western blotting, q-PCR, immunofluorescence, and functional evaluation suggested that glial fibrillary acidic protein (GFAP) expression decreased in the lesion area, the porosity of the scar increased, and remyelination enhanced. Mice overexpressing the transcription factors OCT4 and KLF4 had higher Basso Mouse Scale scores than did the control mice. Moreover, using immunofluorescence and Western blotting, we discovered that some astrocytes expressed nestin and sox2 protein, suggesting that these astrocytes were reprogrammed into neural stem cell-like cells. Furthermore, a cell scratch assay showed that the migration ability of the astrocytes was significantly inhibited in the presence of the transcription factors OCT4 and KLF4. In addition, we demonstrated that the Hippo/Yap pathway was activated after these two transcription factors overexpressed in astrocytes. Conclusions In summary, these results suggest that overexpression of the transcription factors OCT4 and KLF4 could induce astrocyte reprogramming, which subsequently improves remyelination and functional recovery after SCI.
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