Adipose mesenchymal stem cell transplantation alleviates spinal cord injury-induced neuroinflammation partly by suppressing the Jagged1/Notch pathway Article Swipe
Zhilai Zhou
,
Xiaobo Tian
,
Mo Biling
,
Huali Xu
,
Yao Shun
,
Zixiang Huang
,
Lishan Huang
,
Huan Xie
,
Liwei Xu
,
Zhang Hui
·
YOU?
·
· 2019
· Open Access
·
· DOI: https://doi.org/10.21203/rs.2.17540/v1
YOU?
·
· 2019
· Open Access
·
· DOI: https://doi.org/10.21203/rs.2.17540/v1
Background The therapeutic effects of adipose-derived mesenchymal stem cell (ADSC) transplantation have been demonstrated in several models of central nervous system (CNS) injury and are thought to involve the modulation of the inflammatory response. However, the exact underlying molecular mechanism is poorly understood. Activation of the Jagged1/Notch signaling pathway is thought to involve inflammatory and gliotic events in the CNS. Here, we elucidated the effect of ADSC transplantation on the inflammatory reaction after spinal cord injury (SCI) and the potential mechanism mediated by Jagged1/Notch signaling pathway suppression.Methods Using a mouse model of compression SCI, ADSCs and Jagged1 small interfering RNA (siRNA) were injected into the spinal cord. Locomotor function, spinal cord tissue morphology and the levels of various proteins and transcripts were compared between groups.Results ADSC treatment resulted in significant downregulation of proinflammatory mediator expression and reduced ionized calcium binding adapter molecule 1 (Iba1) and ED1 staining in the injured spinal cord, promoting the survival of neurons. These changes were accompanied by improved functional recovery. The augmentation of the Jagged1/Notch signaling pathway after SCI was suppressed by ADSC transplantation. The inhibition of the Jagged1/Notch signaling pathway by Jagged1 siRNA resulted in a decrease in SCI-induced proinflammatory cytokines as well as the activation of microglia. Furthermore, Jagged1 knockdown suppressed the phosphorylation of JAK/STAT3 following SCI.Conclusion The results of this study demonstrated that the therapeutic effects of ADSCs in SCI mice were partly due to Jagged1/notch signaling pathway inhibition and a subsequent reduction in JAK/STAT3 phosphorylation.
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- Type
- preprint
- Language
- en
- Landing Page
- https://doi.org/10.21203/rs.2.17540/v1
- https://assets.researchsquare.com/files/rs-8172/v1/manuscript.pdf
- OA Status
- green
- Cited By
- 3
- References
- 20
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W4242661354
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Raw OpenAlex JSON
- OpenAlex ID
-
https://openalex.org/W4242661354Canonical identifier for this work in OpenAlex
- DOI
-
https://doi.org/10.21203/rs.2.17540/v1Digital Object Identifier
- Title
-
Adipose mesenchymal stem cell transplantation alleviates spinal cord injury-induced neuroinflammation partly by suppressing the Jagged1/Notch pathwayWork title
- Type
-
preprintOpenAlex work type
- Language
-
enPrimary language
- Publication year
-
2019Year of publication
- Publication date
-
2019-11-22Full publication date if available
- Authors
-
Zhilai Zhou, Xiaobo Tian, Mo Biling, Huali Xu, Yao Shun, Zixiang Huang, Lishan Huang, Huan Xie, Liwei Xu, Zhang HuiList of authors in order
- Landing page
-
https://doi.org/10.21203/rs.2.17540/v1Publisher landing page
- PDF URL
-
https://assets.researchsquare.com/files/rs-8172/v1/manuscript.pdfDirect link to full text PDF
- Open access
-
YesWhether a free full text is available
- OA status
-
greenOpen access status per OpenAlex
- OA URL
-
https://assets.researchsquare.com/files/rs-8172/v1/manuscript.pdfDirect OA link when available
- Concepts
-
Notch signaling pathway, Proinflammatory cytokine, Transplantation, Neuroinflammation, Spinal cord injury, Mesenchymal stem cell, Cell biology, Signal transduction, Cancer research, Biology, Medicine, Immunology, Neuroscience, Spinal cord, Internal medicine, InflammationTop concepts (fields/topics) attached by OpenAlex
- Cited by
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3Total citation count in OpenAlex
- Citations by year (recent)
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2023: 2, 2021: 1Per-year citation counts (last 5 years)
- References (count)
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20Number of works referenced by this work
- Related works (count)
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10Other works algorithmically related by OpenAlex
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