Squamous cell carcinoma antigen-1/SerpinB3 is an endogenous skin injury response element.

IF 9.1 1区综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES

Proceedings of the National Academy of Sciences of the United States of America Pub Date : 2025-10-23 DOI:10.1073/pnas.2415164122

Jordan R Yaron,Shubham Pallod,Sepideh Nezhadi,Holly M Gildar,Jayda Hylton-Pelaia,Jordan Roberts,Jacquelyn Kilbourne,Kaushal Rege

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Abstract

The squamous cell carcinoma antigen SerpinB3 is a serum-circulating biomarker of epithelial cancers associated with high metastasis, treatment resistance, and poor prognosis. Despite its clinical significance, the endogenous role of SerpinB3 has remained undefined. Here, we identify SerpinB3 as a mediator of epithelial wound healing. Injury induces SerpinB3 expression in vitro and in vivo in the migrating epidermal tongue; overexpression of the protein promotes epithelial-to-mesenchymal transition-like changes. Recombinant Serpinb3a, the mouse ortholog, enhances re-epithelialization in vitro and accelerates wound closure and collagen remodeling in vivo. These findings reveal a physiological function for SerpinB3 in epithelial repair and suggest that its expression in cancer, chronic wounds, and inflammatory diseases may reflect reactivation of a conserved wound response program-positioning SerpinB3 as a compelling therapeutic target.

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鳞状细胞癌抗原-1/SerpinB3是一种内源性皮肤损伤反应因子。

鳞状细胞癌抗原SerpinB3是一种血清循环生物标志物，与高转移、治疗耐药和预后差相关的上皮癌。尽管具有临床意义，SerpinB3的内源性作用仍未明确。在这里，我们确定SerpinB3是上皮伤口愈合的介质。损伤诱导迁移表皮舌组织中SerpinB3的体内外表达；该蛋白的过度表达促进上皮细胞向间质细胞转变样的变化。重组Serpinb3a，小鼠同源物，在体外增强再上皮化，在体内加速伤口愈合和胶原重塑。这些发现揭示了SerpinB3在上皮修复中的生理功能，并表明其在癌症、慢性伤口和炎症性疾病中的表达可能反映了保守的伤口反应程序的再激活，将SerpinB3定位为一个令人信服的治疗靶点。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Proceedings of the National Academy of Sciences of the United States of America 综合性期刊-综合性期刊

CiteScore

19.00

自引率

0.90%

发文量

3575

审稿时长

2.5 months

期刊介绍： The Proceedings of the National Academy of Sciences (PNAS), a peer-reviewed journal of the National Academy of Sciences (NAS), serves as an authoritative source for high-impact, original research across the biological, physical, and social sciences. With a global scope, the journal welcomes submissions from researchers worldwide, making it an inclusive platform for advancing scientific knowledge.