Notch1 promotes mouse spinal neural stem and progenitor cells proliferation via p-p38-pax6 induced cyclin D1 activation

Journal Article · Sat Dec 15 04:00:00 EST 2018 · Experimental Cell Research

DOI:https://doi.org/10.1016/J.YEXCR.2018.09.025· OSTI ID:23082334

Wang, Rui ^[1]; Zhao, Chenguang ^[2]; Li, Jianjun ^[3]; Li, Yuhuan ^[1]; Liu, Ying ^[4]; others, and

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1. The Department of Orthopedics, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi Province, PR of (China)
2. The Department of Rehabilitation, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi Province, PR of (China)
3. The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an, Shaanxi Province, PR of (China)
4. The Department of Education, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi Province, PR of (China)

Highlights: • Notch1 promotes the proliferation of adult mouse spinal cord derived NSPCs. • Notch1 regulates NSPC proliferation via the p-p38-pax6 pathway. • Pax6 upregulates cyclin D1 expression, inducing the transition of NSPCs to S-phase. Neural stem and progenitor cells (NSPCs) are important for nerve regeneration after spinal cord injury (SCI). Their proliferation, however, is limited. In this study, we investigated the role of Notch1 signaling in NSPC proliferation using adult mouse spinal cord derived NSPCs. We observed that Notch1 promoted proliferation of NSPCs and that Notch1 overexpression led to an expansion of cells in the S-phase and increased cyclin D1 expression. When investigating the functional relationship between Notch1, p-p38 and Pax6, we found that Notch1 suppressed p-p38 while promoting Pax6 expression. Functional inhibition of p38 with SB202190 led to increased Pax6 expression and to proliferation, as determined by BrdU. Furthermore, we confirmed that Pax6 induced proliferation in adult mouse spinal cord derived NSPCs. In conclusion, we demonstrate that Notch1 promotes the proliferation of mouse spinal NSPCs via a p-p38-pax6-cyclin D1 signaling pathway. This pathway constitutes a promising new therapeutic target for SCI treatment.

• OSTI ID: 23082334
• Journal Information: Experimental Cell Research, Journal Name: Experimental Cell Research Journal Issue: 1-2 Vol. 373; ISSN 0014-4827; ISSN ECREAL
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
CELL PROLIFERATION
MICE
NERVES
SPINAL CORD