Inhibition of SENP5 reduces brain injury in TBI rats by regulating NEDD4L/TCF3 axis

Abstract

Background

The underlying mechanism of SENP5 influences neuronal regeneration and apoptosis in the context of TBI remains largely unexplored.

Methods

In the present study, PC12 cells treated with scratch for 24 h were regarded as a TBI cell model. The expression of SENP5 in PC12 cells was measured via Quantitative Real-Time PCR (qRT-PCR) and western blot assays. Cell Counting Kit 8 (CCK–8) and Flow cytometry assays were used to evaluate the activity of TBI cells. In addition, we assessed the effect of inhibiting SENP5 in vivo on neurological function deficits and apoptosis in the hippocampal tissues of TBI rats. The relationship between SENP5 and NEDD4L/TCF3 axis was proved via immunoprecipitation (IP) and double luciferase assays.

Results

Following TBI cell modeling, an increase in SENP5 expression has been found. Moreover, TBI modeling resulted in reduced cell viability and increased apoptosis, which was rescue by inhibition of SENP5. In vivo experiments demonstrated that SENP5 inhibition could mitigate TBI-induced brain injury in rats. Specifically, this inhibition led to lower neurological impairment scores, improved neuronal morphology and structure, and decreased neuronal apoptosis. In addition, NEDD4L has been proved to be relevant to the enhanced stability of the transcription factor TCF3, which in turn promoted the expression of SENP5.

Conclusions

This study reveals that inhibiting SENP5 can alleviate brain injury following TBI. NEDD4L/TCF3 axis can regulate the expression of SENP5 to affect the development of TBI. However, SENP5 regulates downstream targets of TBI and important mechanisms need to be further explored.

Keywords:

• Traumatic brain injury
• NEDD4L
• TCF3
• SENP5

Author contributions

Minjun Wei and Hai Luo designed the experiments. Minjun Wei, Tao Hong and Ying Liu performed the experiments. Minjun Wei and Hai Luo contributed to data analyses. Minjun Wei and Hai Luo drafted this manuscript. Hai Luo reviewed and edited the manuscript. all authors interpreted the data, revised the manuscript, approved the final content, and read and approved the final manuscript. all authors contributed to the article and approved the submitted version.

Consent for publication

All authors consent for publication.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Ethics approval

The experiments were performed by the guidelines of the Experimental animal Management and Ethics Committee of Nanchang University. The protocol number is (K–2022–0123–1).

Data availability statement

The datasets used and/or analyzed during the current study are available from the corresponding author upon reasonable request.

Additional information

Funding

Not application.