Knockdown of ANXA3 regulates NF-κB/STAT3 pathway to alleviate inflammation and hyperproliferation in psoriasis models
Main Article Content
Keywords
Annexin A3 (ANXA3), inflammation, NF-κB/STAT3 pathway, psoriasis, skin
Abstract
Psoriasis is an immune-mediated inflammatory skin disorder and its pathological mechanism remains incompletely understood. Detailed exploration of this mechanism is crucial to identify key regulatory molecules influencing its progression. In previous studies, Annexin A3 (ANXA3), a calcium-dependent phospholipid-binding protein from the annexin family, has been linked to psoriasis progression. However, its specific effects on the disease remain unclear. This study aimed to investigate the role of ANXA3 in psoriasis progression. For this purpose, we employed an imiquimod (IMQ)-induced mouse model and in-vitro experiments to uncover the underlying cellular mechanisms. A mixture of five inflammatory factors (TNF-α, IL-1α, IL-17A, IL-22, and statin M) was used to stimulate HaCaT cells, mimicking the psoriasis microenvironment. Our findings demonstrate that ANXA3 is highly expressed in psoriatic skin, and its knockdown alleviates skin lesions in IMQ-induced mice. Further analysis revealed that ANXA3 knockdown reduces skin tissue hyperplasia and decreases the expression of inflammatory factors in IMQ mice. Mechanistically, ANXA3 knockdown inhibits the NF-κB/STAT3 pathway in skin tissue. Additionally, ANXA3 knockdown inhibits inflammation and hyperproliferation in HaCaT cells. Collectively, these results indicate that ANXA3 alleviates psoriasis progression both in-vivo and in-vitro by inhibiting the NF-κB/STAT3 pathway.
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