# NAT10 Regulates LPS-Induced Inflammation via Stabilization of N4-Acetylated PTX3 mRNA in Human Dental Pulp Stem Cells

## TL;DR

This study shows that NAT10 promotes inflammation in dental pulp stem cells by stabilizing PTX3 mRNA, and blocking NAT10 could help treat pulpitis.

## Contribution

The study reveals NAT10's role in regulating inflammation via PTX3 mRNA stabilization in human dental pulp stem cells.

## Key findings

- NAT10 knockdown reduces inflammatory gene expression and ROS production in LPS-stimulated hDPSCs.
- PTX3 mRNA stability and expression decrease in NAT10-deficient cells, linking it to reduced inflammation.
- Remodelin, a NAT10 inhibitor, attenuates dental pulp inflammation in a rat model of pulpitis.

## Abstract

Severe dental pulp inflammation can lead to tissue lysis and destruction, underscoring the necessity for effective treatment of pulpitis. N-acetyltransferase 10 (NAT10)-mediated N4-acetylcytidine (ac4C) modification has recently emerged as a key regulator in inflammatory processes. However, whether NAT10 affects the inflammatory response in human dental pulp stem cells (hDPSCs) remains unelucidated. In this study, elevated NAT10 expression was observed in pulpitis tissues and LPS-stimulated hDPSCs. Knockdown of NAT10 led to reduced inflammatory gene expression and lower reactive oxygen species (ROS) production in LPS-stimulated hDPSCs, while the chemotactic migration of macrophages was also suppressed. Similar results were observed when hDPSCs were treated with Remodelin, an inhibitor of NAT10. Differentially expressed genes identified through RNA sequencing were significantly enriched in inflammatory signaling pathways after NAT10 depletion. Among the differential genes, pentraxins 3 (PTX3) was identified as the potential target gene due to the presence of the ac4C modification site and its known ability to regulate dental pulp inflammation. The mRNA and protein levels of PTX3 were reduced in NAT10-deficient cells, along with a decrease in its mRNA stability. Exogenous PTX3 supplementation partially reversed the inflammatory inhibition induced by NAT10 knockdown. Further evidence in vivo revealed that Remodelin treatment attenuated the severity of dental pulp inflammation in rats with pulpitis. In summary, these data indicated that NAT10 deficiency inhibited the stability of PTX3 mRNA and further inhibited hDPSC inflammation, while Remodelin might be a potential therapeutic agent for pulp capping.