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Article ; Online: Repair of Spinal Cord Injury by Inhibition of PLK4 Expression Through Local Delivery of siRNA-Loaded Nanoparticles.

Gu, Yingchu / Zhang, Runze / Jiang, Bin / Xu, Xin / Guan, Jun Jie / Jiang, Xing Jie / Zhou, Yuan / Zhou, You Lang / Chen, Xiangdong

Journal of molecular neuroscience : MN

2021  Volume 72, Issue 3, Page(s) 544–554

Abstract: Polo-like kinase 4 (PLK4) is one of the key regulators of centrosomal replication. However, its role and mechanism in spinal cord injury (SCI) are still unclear. The SCI model on rats was constructed and the expression and localization of PLK4 in the ... ...

Abstract Polo-like kinase 4 (PLK4) is one of the key regulators of centrosomal replication. However, its role and mechanism in spinal cord injury (SCI) are still unclear. The SCI model on rats was constructed and the expression and localization of PLK4 in the spinal cord are analyzed with Western blot and immunofluorescence, respectively. Then the specific siRNAs were encapsulated in nanoparticles for the inhibition of PLK4 expression. Afterward, the role of PLK4 on astrocytes was investigated by knocking down its expression in the primary astrocytes. Moreover, siRNA-loaded nanoparticles were injected into the injured spinal cord of rats, and the motor function recovery of rats after SCI was assessed using the Basso, Beattie, and Bresnahan (BBB) locomotor scale method. Notably, the siRNA-loaded nanoparticles effectively transfect primary astrocytes and significantly inhibit PLK4 expression, together with the expression of PCNA with significance. After treatment, restoration of the motor function following SCI was significantly improved in the PLK4 knockdown group compared with the control group. Therefore, we speculate that inhibition of Plk4 may inhibit the proliferation of astrocytes and decrease the inflammatory response mediated by astrocytes, so as to promote the functional recovery of SCI. In conclusion, inhibition of PLK4 expression via siRNA-loaded nanoparticles may be a potential treatment for SCI.
MeSH term(s) Animals ; Nanoparticles ; RNA, Small Interfering/genetics ; Rats ; Rats, Sprague-Dawley ; Recovery of Function/physiology ; Spinal Cord/metabolism ; Spinal Cord Injuries/genetics ; Spinal Cord Injuries/metabolism ; Spinal Cord Injuries/therapy
Chemical Substances RNA, Small Interfering
Language English
Publishing date 2021-09-01
Publishing country United States
Document type Journal Article
ZDB-ID 1043392-2
ISSN 1559-1166 ; 0895-8696
ISSN (online) 1559-1166
ISSN 0895-8696
DOI 10.1007/s12031-021-01871-1
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