NAT10 aggravates psoriasis by promoting keratinocytes fatty acid synthesis via stable FASN transcription

Weibo Tang; Jingling Shen; Jiaxin Liu; Chunhui Jiang; Wenya Liu; Mengyao Xiao; Jindan Dai; Wenjie Gao; Junjie Lu; Chunyi Hu; Yonghuan Song; Ye Xu; Zhongxin Zhu; Weitao Cong

doi:10.1016/j.jpha.2026.101590

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Article Navigation > Journal of Pharmaceutical Analysis > 2026 > Accepted Manu

Weibo Tang, Jingling Shen, Jiaxin Liu, Chunhui Jiang, Wenya Liu, Mengyao Xiao, Jindan Dai, Wenjie Gao, Junjie Lu, Chunyi Hu, Yonghuan Song, Ye Xu, Zhongxin Zhu, Weitao Cong. NAT10 aggravates psoriasis by promoting keratinocytes fatty acid synthesis via stable FASN transcription[J]. Journal of Pharmaceutical Analysis. doi: 10.1016/j.jpha.2026.101590

Citation:

Weibo Tang, Jingling Shen, Jiaxin Liu, Chunhui Jiang, Wenya Liu, Mengyao Xiao, Jindan Dai, Wenjie Gao, Junjie Lu, Chunyi Hu, Yonghuan Song, Ye Xu, Zhongxin Zhu, Weitao Cong. NAT10 aggravates psoriasis by promoting keratinocytes fatty acid synthesis via stable FASN transcription[J]. Journal of Pharmaceutical Analysis. doi: 10.1016/j.jpha.2026.101590

Citation:

Weibo Tang, Jingling Shen, Jiaxin Liu, Chunhui Jiang, Wenya Liu, Mengyao Xiao, Jindan Dai, Wenjie Gao, Junjie Lu, Chunyi Hu, Yonghuan Song, Ye Xu, Zhongxin Zhu, Weitao Cong. NAT10 aggravates psoriasis by promoting keratinocytes fatty acid synthesis via stable FASN transcription[J]. Journal of Pharmaceutical Analysis. doi: 10.1016/j.jpha.2026.101590

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NAT10 aggravates psoriasis by promoting keratinocytes fatty acid synthesis via stable FASN transcription

doi: 10.1016/j.jpha.2026.101590

a. State Key Laboratory of Macromolecular Drugs and Large-scale Manufacturing, School of Pharmaceutical Science, Wenzhou Medical University, Wenzhou, Zhejiang, 325000, China;
b. Translational Medicine Laboratory, Jilin Medical University, Jilin, Jilin, 132013, China;
c. Institute of Life Sciences, College of Life and Environmental Sciences, Wenzhou University, Wenzhou, Zhejiang, 325000, China;
d. Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325027, China

Funds:

This work was supported by the Natural Science Foundation of Jilin Province (Grant No.: YDZJ202201ZYTS286) and the National Nature Science Foundation of China (Grant Nos.: 82272284, and 82370297). We thank Scientific Research Center of Wenzhou Medical University for providing excellent consultation and instrumental supports. We also sincerely thank Prof. Hengyu Fan (Zhejiang University) for generously providing the NAT10^flox/flox transgenic mice.

Received Date: Sep. 27, 2025
Accepted Date: Feb. 15, 2026
Rev Recd Date: Feb. 14, 2026
Available Online: Feb. 28, 2026

Abstract

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.
- NAT10,
- psoriasis,
- proliferation,
- fatty acid synthase,
- ac4C modification

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References(48)

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