ZNF521 Overexpression in U87MG Cells Induces Neural Progenitors and Improves Motor Function in Spinal Cord Injury in Rats

Document Type : Original Research

Authors
S. D. Alizadeh 1
Z. Ghodsi 2
J. S. Harrop 3
S. M. Ghodsi 2
N. Rahimimovaghar 4
V. Rahimi-Movaghar 5
1 Sina Trauma and Surgery Research Center, Tehran University of Medical Sciences, Tehran, Iran
2 1. Sina Trauma and Surgery Research Center, Tehran University of Medical Sciences, Tehran, Iran2. Brain and Spinal Cord Injury Research Center, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Iran
3 Department of Neurosurgery, Thomas Jefferson University, Philadelphia, Pennsylvania, USA
4 Department of Psychology, Western Carolina University (WCU), Cullowhee, NC, USA
5 Sina Trauma and Surgery Research Center, Tehran University of Medical Sciences, Tehran, Iran.
Abstract
Introduction: This experimental in-vitro and in-vivo parallel-group study aimed to investigate the ZNF521 overexpression effects on the glioblastoma cell line (U87MG) behavior in vitro and the therapeutic potential of U87MG cells that were overexpressed by ZNF521 (U87-ZNF521) in functional recovery of spinal cord injury (SCI) in rats.

Methods: ZNF521-IRES-GFP was introduced into U87MG cells and maintained in the neural inductive medium for over 3 weeks. The GFAP, ITGA6, PAX6, NES, SOX1, TUBB3, and OLIG2 gene expressions were analyzed. The SCI rats were split into three groups, with 10 rats each (30 rats in total). Then, U87-ZNF521 cells were transplanted, and the Basso-Beattie-Bresnahan scale and footprint analysis were used to evaluate the rats’ locomotor capacity.

Results: ZNF521 overexpression induced morphological changes and aggregated formation in U87MG cells, with a 26% transfection rate. Significant upregulation of PAX6, TUBB3, and OLIG2 and decreasing SOX1 were observed, while GFAP, ITGA6, and NES showed non-significant changes compared to the control group. In SCI rats, U87-ZNF521 exhibited substantial recovery in hindlimb motor coordination and weight support. Moreover, gait analysis revealed increased step length, stride angle, and step width in U87-ZNF521 rats during a five-week treatment. However, no significant improvement was observed with plantar application.

Conclusion: ZNF521 overexpression in the U87MG suggests its potential to differentiate into neural progenitors. Additionally, these neural progenitors improved motor function in SCI rats. ZNF521 can be a potential therapy for promoting recovery in glioblastoma and SCIs, highlighting its role as a promising target for further exploration in neural regeneration strategies.

Keywords

Subjects

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Pathobiology Reserach
Volume 28, Issue 2
March 2025
Pages 51-62