RNF20 deletion causes inflammation in model of sepsis through the NLRP3 activation

Abstract

Aim: Sepsis is an extremely complex, threatening and difficult-to-treat disease, which can occur at any age and under any underlying disease. RNF20 regulate NF-kappaB (NF-κB) signaling pathway and the transcription of inflammatory factors of target genes. Therefore, it is of great significance to study the function of RNF20 in the clinical treatment of sepsis and its underlying mechanisms.

Methods: C57BL/6 mice were subjected to cecal ligation and puncture (CLP) surgery. THP-1 cells were induced with Lipopolysaccharide for 4 h.

Results: RNF20 gene, mRNA expression and protein expression were reduced in patients with sepsis and mice with sepsis. Based on RNF20 deletion (RNF20^-/-) mice, these were found to be increased inflammation reactions in RNF20^-/- mice. However, the RNF20 human protein reduced inflammation reactions in mice with sepsis. In vitro model of sepsis, over-expression of RNF20 inhibited inflammation reactions by inducing Vitamin D Receptor (VDR), while down-regulation of RNF20 promoted inflammation reactions through the suppression of VDR. RNF20 protein was interlinked with VDR protein, and VDR protein was also interlinked with NLRP3. Furthermore, VDR promoted NLRP3 ubiquitination and reduced NLRP3 function in vitro model of sepsis.

Conclusion: These studies demonstrate that RNF20 suppressed inflammation reactions in models with sepsis through NLRP3 inflammasome and NLRP3 ubiquitination by activating VDR.

Keywords:

• Sepsis
• NLRP3
• RNF20
• ubiquitination
• vitamin D receptor

Authors’ contributions

ALQ and YCL designed the experiments. JHZ, YTW, and WL performed the experiments. TW and YFC collected and analyzed the data. TW and YFC drafted the manuscript. All authors read and approved the final manuscript.

Ethical statement

All patients were informed and signed informed consent voluntarily. This study was approved by the ethics committee of the Tianjin Medical University General Hospital and complied with the guidelines outlined in the Declaration of Helsinki were followed.

Patient consent

Written consent was received from all participants.

Consent for publication

Not applicable.

Disclosure statement

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

Data availability

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

Additional information

Funding

Scientific Research Project of Tianjin Education Commission [2019KJ200].