Knockdown of ANXA3 regulates NF-κB/STAT3 pathway to alleviate inflammation and hyperproliferation in psoriasis models

Area of Science:

• Dermatology
• Immunology
• Molecular Biology

Background:

• Psoriasis is a complex immune-mediated inflammatory skin disorder with incompletely understood pathological mechanisms.
• Identifying key regulatory molecules is crucial for understanding psoriasis progression.
• Annexin A3 (ANXA3) has been previously linked to psoriasis, but its specific role requires further elucidation.

Purpose of the Study:

• To investigate the role of Annexin A3 (ANXA3) in the progression of psoriasis.
• To uncover the underlying cellular and molecular mechanisms by which ANXA3 influences psoriasis.

Main Methods:

• Utilized an imiquimod (IMQ)-induced mouse model of psoriasis.
• Employed in vitro experiments using HaCaT cells stimulated with a mixture of inflammatory factors (TNF-α, IL-1α, IL-17A, IL-22, and statin M) to mimic the psoriatic microenvironment.
• Assessed the effects of ANXA3 knockdown on skin lesions, hyperplasia, inflammatory factor expression, and the NF-κB/STAT3 signaling pathway.

Main Results:

• ANXA3 was found to be highly expressed in psoriatic skin lesions.
• ANXA3 knockdown significantly alleviated skin lesions and reduced skin tissue hyperplasia in IMQ-induced mice.
• ANXA3 knockdown suppressed the expression of inflammatory factors and inhibited the NF-κB/STAT3 pathway in both in vivo and in vitro models.
• ANXA3 knockdown reduced inflammation and hyperproliferation in HaCaT cells.

Conclusions:

• Annexin A3 (ANXA3) promotes psoriasis progression.
• ANXA3 inhibition represents a potential therapeutic strategy for psoriasis by modulating the NF-κB/STAT3 pathway.
• Targeting ANXA3 could effectively alleviate psoriatic inflammation and hyperproliferation.