2. Academic Validation
  3. Fibrotic matrix induces mesenchymal transformation of epithelial cells in oral submucous fibrosis

Fibrotic matrix induces mesenchymal transformation of epithelial cells in oral submucous fibrosis

  • Am J Pathol. 2023 Jun 14;S0002-9440(23)00208-0. doi: 10.1016/j.ajpath.2023.05.014.
Hao-Qing Xu 1,  Zhen-Xing Guo 2,  Jian-Fei Yan 2,  Shu-Yan Wang 2,  Jia-Lu Gao 2,  Xiao-Xiao Han 1,  Wen-Pin Qin 2,  Wei-Cheng Lu 2,  Chang-He Gao 3,  Wei-Wei Zhu 1,  Yu-Tong Fu 1,  Kai Jiao 4
Affiliations

Affiliations

  • 1 The college of life science Northwest University, Xi'an, Shaanxi, P.R. China; Department of Stomatology, Tangdu hospital, The Fourth Military Medical University, Xi'an, Shaanxi, P.R. China; State Key Laboratory of Stomatognathic Reconstruction and Regeneration & National Clinical Research Center for Oral Diseases & Shaanxi Key Laboratory of Stomatology, School of Stomatology, The Fourth Military Medical University, Xi'an, Shaanxi, P.R. China.
  • 2 Department of Stomatology, Tangdu hospital, The Fourth Military Medical University, Xi'an, Shaanxi, P.R. China; State Key Laboratory of Stomatognathic Reconstruction and Regeneration & National Clinical Research Center for Oral Diseases & Shaanxi Key Laboratory of Stomatology, School of Stomatology, The Fourth Military Medical University, Xi'an, Shaanxi, P.R. China.
  • 3 Department of Stomatology, Tangdu hospital, The Fourth Military Medical University, Xi'an, Shaanxi, P.R. China; State Key Laboratory of Stomatognathic Reconstruction and Regeneration & National Clinical Research Center for Oral Diseases & Shaanxi Key Laboratory of Stomatology, School of Stomatology, The Fourth Military Medical University, Xi'an, Shaanxi, P.R. China; The Third Affiliated Hospital of Xinxiang Medical University, Xinxiang, P.R. China.
  • 4 Department of Stomatology, Tangdu hospital, The Fourth Military Medical University, Xi'an, Shaanxi, P.R. China; State Key Laboratory of Stomatognathic Reconstruction and Regeneration & National Clinical Research Center for Oral Diseases & Shaanxi Key Laboratory of Stomatology, School of Stomatology, The Fourth Military Medical University, Xi'an, Shaanxi, P.R. China. Electronic address: kjiao1@163.com.
PMID: 37328100 DOI: 10.1016/j.ajpath.2023.05.014
Abstract

Oral submucous fibrosis (OSF) is a potentially malignant disorder of the oral mucosa; however, whether and how the fibrotic matrix of OSF is involved in the malignant transformation of epithelial cells remains unknown. Herein, oral mucosa tissue from patients with OSF, OSF rat models, and their controls were used to observe the extracellular matrix changes and epithelial-mesenchymal transformation (EMT) in fibrotic lesions. Compared with the controls, oral mucous tissues from patients with OSF exhibited increased number of myofibroblasts, decreased number of blood vessels and increased type I and type III collagen levels. In addition, the oral mucous tissues from humans and OSF rats showed increased stiffness, accompanied by increased EMT activities of epithelial cells. The EMT activities of stiff construct-cultured epithelial cells were significantly increased by exogenous Piezo1 activation, and decreased by YAP inhibition. During ex vivo implantation, oral mucosal epithelial cells of the stiff group showed increased EMT activities and increased levels of Piezo1 and YAP compared with those in the sham and soft groups. We concluded that increased stiffness of the fibrotic matrix in OSF led to increased proliferation and EMT of mucosal epithelial cells, in which the Piezo1-YAP signal transduction is important.

Keywords

Extracellular matrix; connective tissue; oral submucous fibrosis; potentially malignant disorder; type Ⅰ collagen; yes-associated protein.

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