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TCN2 Drives Psoriasis-Like Inflammation and Keratinocyte Hyperproliferation, Correlating With IL-1β and STAT3
Jing-Kai Xu1,2, Xin-Zhu Zhou3, Ke Xue1
1Department of Dermatology, China-Japan Friendship Hospital, Beijing, China.
Summary
Transcobalamin 2 (TCN2) drives psoriasis by promoting skin cell overgrowth and inflammation. Reducing TCN2 may offer a new therapeutic strategy for this chronic immune disorder.
Area of Science:
- Dermatology
- Immunology
- Molecular Biology
Background:
- Psoriasis is a chronic immune-mediated inflammatory disease.
- The role of transcobalamin 2 (TCN2) in psoriasis pathogenesis is not well understood.
Purpose of the Study:
- To investigate the role of TCN2 in the development and progression of psoriasis.
- To explore TCN2 as a potential therapeutic target for psoriasis.
Main Methods:
- Quantified TCN2 expression in lesional skin and peripheral blood mononuclear cells (PBMCs) from psoriasis patients and in a mouse model.
- Utilized imiquimod (IMQ)-induced psoriasis model in wild-type and Tcn2-deficient mice.
- Performed transcriptomic analysis of lesional skin and assessed keratinocyte proliferation and inflammatory factor expression in TCN2-knockdown cells.
Main Results:
- TCN2 expression was significantly elevated in psoriasis patients and IMQ-induced mouse models.
- Tcn2-deficient mice exhibited attenuated skin lesions with reduced inflammation and epidermal hyperplasia.
- TCN2 deficiency led to downregulation of key inflammatory mediators and suppression of STAT3 signaling, while TCN2 knockdown impaired keratinocyte proliferation.
Conclusions:
- TCN2 plays a critical role in promoting keratinocyte hyperproliferation and amplifying inflammatory responses in psoriasis.
- TCN2 is identified as a novel regulator of psoriatic inflammation and keratinocyte biology.
- TCN2 represents a potential novel therapeutic target for psoriasis treatment.
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