NAT10 aggravates psoriasis by promoting keratinocytes fatty acid synthesis via stable FASN transcription
7 affiliations
- 1State Key Laboratory of Macromolecular Drugs and Large-scale Manufacturing, School of Pharmaceutical Science, Wenzhou Medical University, Wenzhou, Zhejiang, 325000, China; Translational Medicine Laboratory, Jilin Medical University, Jilin, Jilin, 132013, China
- 2Institute of Life Sciences, College of Life and Environmental Sciences, Wenzhou University, Wenzhou, Zhejiang, 325000, China
- 3Translational Medicine Laboratory, Jilin Medical University, Jilin, Jilin, 132013, China
- 4State Key Laboratory of Macromolecular Drugs and Large-scale Manufacturing, School of Pharmaceutical Science, Wenzhou Medical University, Wenzhou, Zhejiang, 325000, China
- 5Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325027, China
- 6Translational Medicine Laboratory, Jilin Medical University, Jilin, Jilin, 132013, China; Corresponding author.
- 7State Key Laboratory of Macromolecular Drugs and Large-scale Manufacturing, School of Pharmaceutical Science, Wenzhou Medical University, Wenzhou, Zhejiang, 325000, China; Corresponding author.
Abstract
RNA modifications have emerged as critical regulators of cellular function and disease pathogenesis; however, their contribution to psoriasis remains unclear. Here, we report that N-acetyltransferase 10 (NAT10) expression is markedly elevated in the epidermis of patients with psoriasis and in imiquimod (IMQ)-induced lesions. Single-cell RNA sequencing further identifies NAT10 upregulation in hyperproliferative and basal keratinocyte subsets. Keratinocyte-specific deletion of NAT10 attenuates IMQ-induced psoriatic phenotypes in mice. Integrative profiling of RNA sequencing and N4-acetylcytidine (ac4C) immunoprecipitation sequencing reveals fatty acid synthase (FASN) as a direct downstream target of NAT10. Mechanistically, NAT10 catalyzes ac4C RNA modification to enhance the stability of FASN mRNA, thereby driving fatty acid metabolic reprogramming and promoting keratinocyte proliferation. This metabolic shift contributes to epidermal hyperplasia and inflammation in psoriasis. Notably, pharmacological inhibition of NAT10 with remodelin alleviates disease severity in vivo and in vitro . Together, these findings identify a NAT10-dependent ac4C regulatory axis that links epitranscriptomic control to metabolic dysregulation in keratinocytes and highlight NAT10 as a promising therapeutic target for psoriasis.
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BibTeX
@article{tang2026nat10,
title = {{NAT10 aggravates psoriasis by promoting keratinocytes fatty acid synthesis via stable FASN transcription}},
author = {Weibo Tang and Jingling Shen and Jiaxin Liu and Chunhui Jiang and Wenya Liu and Mengyao Xiao and Jindan Dai and Wenjie Gao and Junjie Lu and Chunyi Hu and Yonghuan Song and Ye Xu and Zhongxin Zhu and Weitao Cong},
journal = {Journal of Pharmaceutical Analysis},
year = {2026},
month = sep,
doi = {10.1016/j.jpha.2026.101590},
url = {https://doi.org/10.1016/j.jpha.2026.101590},
note = {CC BY},
}
RIS
TY - JOUR
TI - NAT10 aggravates psoriasis by promoting keratinocytes fatty acid synthesis via stable FASN transcription
AU - Weibo Tang
AU - Jingling Shen
AU - Jiaxin Liu
AU - Chunhui Jiang
AU - Wenya Liu
AU - Mengyao Xiao
AU - Jindan Dai
AU - Wenjie Gao
AU - Junjie Lu
AU - Chunyi Hu
AU - Yonghuan Song
AU - Ye Xu
AU - Zhongxin Zhu
AU - Weitao Cong
PY - 2026
DA - 2026/09/01
JO - Journal of Pharmaceutical Analysis
DO - 10.1016/j.jpha.2026.101590
UR - https://doi.org/10.1016/j.jpha.2026.101590
AB - RNA modifications have emerged as critical regulators of cellular function and disease pathogenesis; however, their contribution to psoriasis remains unclear. Here, we report that N-acetyltransferase 10 (NAT10) expression is markedly elevated in the epidermis of patients with psoriasis and in imiquimod (IMQ)-induced lesions. Single-cell RNA sequencing further identifies NAT10 upregulation in hyperproliferative and basal keratinocyte subsets. Keratinocyte-specific deletion of NAT10 attenuates IMQ-induced psoriatic phenotypes in mice. Integrative profiling of RNA sequencing and N4-acetylcytidine (ac4C) immunoprecipitation sequencing reveals fatty acid synthase (FASN) as a direct downstream target of NAT10. Mechanistically, NAT10 catalyzes ac4C RNA modification to enhance the stability of FASN mRNA, thereby driving fatty acid metabolic reprogramming and promoting keratinocyte proliferation. This metabolic shift contributes to epidermal hyperplasia and inflammation in psoriasis. Notably, pharmacological inhibition of NAT10 with remodelin alleviates disease severity in vivo and in vitro . Together, these findings identify a NAT10-dependent ac4C regulatory axis that links epitranscriptomic control to metabolic dysregulation in keratinocytes and highlight NAT10 as a promising therapeutic target for psoriasis.
SN - 2095-1779
SN - 2214-0883
ER -