2. Academic Validation
  3. Matrix metalloproteinase-9 upregulation in keratinocytes of oral lichen planus via c-Jun N-terminal kinase signaling pathway activation

Matrix metalloproteinase-9 upregulation in keratinocytes of oral lichen planus via c-Jun N-terminal kinase signaling pathway activation

  • J Dent Sci. 2025 Jan;20(1):302-309. doi: 10.1016/j.jds.2024.07.010.
Xinke Jiang 1 2,  Yiwen Deng 1 2,  Yirao Lai 1 2,  Guanhuan Du 1 2,  Xiye Li 1 2,  Xiaojie Yang 1 2,  Mingya Li 3,  Lei Sun 3,  Yufeng Wang 1 2,  Guoyao Tang 1 2 4
Affiliations

Affiliations

  • 1 Department of Oral Medicine, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
  • 2 College of Stomatology, Shanghai Jiao Tong University, National Center for Stomatology, National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology, Shanghai, China.
  • 3 Institute of Developmental Biology and Molecular Medicine, Fudan University, Shanghai, China.
  • 4 Department of Stomatology, Xin Hua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
PMID: 39873082 DOI: 10.1016/j.jds.2024.07.010
Abstract

Background/purpose: Oral Lichen planus (OLP) is a chronic inflammatory disorder characterized by basement membrane disruption, which plays a crucial role in its pathogenesis. Matrix Metalloproteinases (MMPs), a group of proteolytic Enzymes, contribute to the degradation of the basement membrane. The specific MMPs secreted by keratinocytes in OLP lesions and relevant regulatory mechanisms are not fully understood. This study aimed to investigate the involvement of MMPs in OLP pathogenesis, focusing on their expression in keratinocytes and regulatory mechanisms.

Materials and methods: MMP mRNA expression in OLP epithelium was analyzed using RNA Sequencing data obtained from the Gene Expression Omnibus (GEO) database. Mucosa samples from 30 OLP patients and 30 healthy controls were collected to observe the expression and regulation of MMPs in keratinocytes. The involvement of the mitogen-activated protein kinase (MAPK) pathway in MMP regulation was studied using HaCaT cells.

Results: RNA Sequencing analysis revealed upregulation of MMP1 and MMP9 in OLP epithelium. MMP9 expression was predominantly observed in basal keratinocytes of OLP lesions. Elevated levels of phosphorylated c-Jun N-terminal kinase (JNK), a component of the MAPK pathway, were detected in OLP samples and co-localized with MMP9 in keratinocytes. Activation of the JNK pathway in HaCaT cells induced MMP9 expression, implicating JNK signaling in MMP9 regulation.

Conclusion: Keratinocytes contribute to OLP pathogenesis by secreting MMP9 through JNK pathway activation. This understanding may provide insights into targeted therapeutic interventions for this chronic recurrent disease.

Keywords

Basement membrane; Keratinocyte; Matrix metalloproteinase; Oral lichen planus; c-Jun N-terminal kinase.

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