MMP12 disrupts epithelial barrier integrity in oral lichen planus by degrading fibronectin

MMP12 通过降解纤连蛋白破坏口腔扁平苔藓上皮屏障的完整性

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作者:Zhouqiao Xie #, Xiangyu Wang #, Xiuyun Ren, Xuejun Ge

Abstract

Oral lichen planus (OLP) is a chronic inflammatory disorder featured with T lymphocytes infiltration and epithelial basement membrane breakdown. Although matrix metalloproteinase-12 (MMP12) is reported to be involved in the pathogenesis of oral diseases such as oral squamous cell carcinoma and periodontitis, the roles of MMP12 in the context of OLP remain poorly understood. Here, we demonstrate that MMP12 in macrophages derived from mucosal diseased tissues compromises the epithelial barrier integrity in OLP. The increased MMP12 facilitates fibronectin degradation in keratinocytes, leading to oral epithelial barrier disruption. Overexpression of fibronectin in oral keratinocytes prevents epithelial barrier from MMP12-induced damage. In addition, pharmacological inhibition of MMP12 reverses keratinocyte barrier disruption in a cell model. Altogether, our study reveals that MMP12 mediates oral epithelial barrier integrity in the setting of OLP.

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