L-Citrulline Attenuates Keratinocyte Activation and Modulates ASS1 Expression in Psoriasis-Like Mice.
- 1Department of Blood Transfusion, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, People's Republic of China.
- 2Department of Cardiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, People's Republic of China.
- 3Department of Blood Transfusion, Fuwai Central China Cardiovascular Hospital, Zhengzhou, People's Republic of China.
Abstract
Purpose
Psoriasis is a common chronic inflammatory skin disease with a high prevalence, which seriously impairs patients' quality of life. Although the clinical application of biologics has achieved satisfactory therapeutic effects, it still has certain limitations, such as high recurrence rate and poor clinical response in some patients. Therefore, it is urgent to further explore the pathogenesis of psoriasis to identify novel research directions and therapeutic targets for the prevention and treatment of this disease.Methods
An imiquimod (IMQ)-induced psoriasis-like mouse model was established in this study. Multi-omics profiling and molecular biological experiments were performed to explore the regulatory mechanism underlying psoriasis progression. Keratinocyte functional assays and pharmacological intervention were conducted to verify the biological function of L-citrulline and ASS1.Results
L-citrulline levels were significantly decreased in the lesional skin of psoriatic mice. L-citrulline treatment substantially alleviated psoriasis-like pathological phenotypes and restrained keratinocyte hyperactivation, including excessive proliferation, migration, and inflammatory responses. Mechanistically, L-citrulline markedly downregulated the expression of ASS1, which was highly upregulated in psoriatic skin lesions. Functional validation demonstrated that ASS1 overexpression promoted keratinocyte activation, whereas pharmacological inhibition of ASS1 efficiently suppressed keratinocyte hyperactivation in vitro and ameliorated IMQ-induced psoriasis-like skin lesions in vivo.Conclusion
ASS1 serves as a critical regulator and promising therapeutic target for psoriasis. L-citrulline supplementation or ASS1 inhibition effectively blocks keratinocyte hyperactivation and retards psoriasis progression, providing a novel and feasible therapeutic strategy for psoriasis treatment.
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BibTeX
@article{yang2026lcitrulline,
title = {{L-Citrulline Attenuates Keratinocyte Activation and Modulates ASS1 Expression in Psoriasis-Like Mice.}},
author = {Shuang Yang and Yang Chen and Zhuli Li and Jinlin Liu and Yanteng Zhao and Xiaoyan Zhang and Qiankun Yang},
journal = {Drug design, development and therapy},
year = {2026},
month = oct,
doi = {10.2147/dddt.s645045},
url = {https://europepmc.org/article/MED/42948665},
note = {CC BY-NC},
}
RIS
TY - JOUR
TI - L-Citrulline Attenuates Keratinocyte Activation and Modulates ASS1 Expression in Psoriasis-Like Mice.
AU - Shuang Yang
AU - Yang Chen
AU - Zhuli Li
AU - Jinlin Liu
AU - Yanteng Zhao
AU - Xiaoyan Zhang
AU - Qiankun Yang
PY - 2026
DA - 2026/10/23
JO - Drug design, development and therapy
DO - 10.2147/dddt.s645045
UR - https://europepmc.org/article/MED/42948665
AB - Purpose Psoriasis is a common chronic inflammatory skin disease with a high prevalence, which seriously impairs patients' quality of life. Although the clinical application of biologics has achieved satisfactory therapeutic effects, it still has certain limitations, such as high recurrence rate and poor clinical response in some patients. Therefore, it is urgent to further explore the pathogenesis of psoriasis to identify novel research directions and therapeutic targets for the prevention and treatment of this disease.Methods An imiquimod (IMQ)-induced psoriasis-like mouse model was established in this study. Multi-omics profiling and molecular biological experiments were performed to explore the regulatory mechanism underlying psoriasis progression. Keratinocyte functional assays and pharmacological intervention were conducted to verify the biological function of L-citrulline and ASS1.Results L-citrulline levels were significantly decreased in the lesional skin of psoriatic mice. L-citrulline treatment substantially alleviated psoriasis-like pathological phenotypes and restrained keratinocyte hyperactivation, including excessive proliferation, migration, and inflammatory responses. Mechanistically, L-citrulline markedly downregulated the expression of ASS1, which was highly upregulated in psoriatic skin lesions. Functional validation demonstrated that ASS1 overexpression promoted keratinocyte activation, whereas pharmacological inhibition of ASS1 efficiently suppressed keratinocyte hyperactivation in vitro and ameliorated IMQ-induced psoriasis-like skin lesions in vivo.Conclusion ASS1 serves as a critical regulator and promising therapeutic target for psoriasis. L-citrulline supplementation or ASS1 inhibition effectively blocks keratinocyte hyperactivation and retards psoriasis progression, providing a novel and feasible therapeutic strategy for psoriasis treatment.
SN - 1177-8881
ER -