TGF-β3 from fibroblasts promotes necrotising sialometaplasia by suppressing salivary gland cell proliferation and inducing squamous metaplasia

J Pathol. 2024 Jul;263(3):338-346. doi: 10.1002/path.6287. Epub 2024 Apr 9.

Abstract

Necrotising sialometaplasia (NSM) is a non-neoplastic lesion mainly arising in the minor salivary glands of the oral cavity. In the clinical features, NSM shows swelling with or without ulceration, and can mimic a malignant disease such as squamous cell carcinoma. Histopathologically, NSM usually shows the lobular architecture that is observed in the salivary glands. Additionally, acinar infarction and squamous metaplasia of salivary ducts and acini are observable. The aetiology of this lesion remains unknown, although it has a characteristic feature that sometimes requires clinical and histopathological differentiation from malignancy. In this study, we investigated upregulated genes in NSM compared with normal salivary glands, and focused on the TGF-β3 (TGFB3) gene. The results of the histopathological studies clarified that fibroblasts surrounding the lesion express TGF-β3. Moreover, in vitro studies using mouse salivary gland organoids revealed that TGF-β3 suppressed salivary gland cell proliferation and induced squamous metaplasia. We demonstrated a possible aetiology of NSM by concluding that increased TGF-β3 expression during wound healing or tissue regeneration played a critical role in cell proliferation and metaplasia. © 2024 The Pathological Society of Great Britain and Ireland.

Keywords: TGF‐β3; necrotising sialometaplasia; salivary gland.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Animals
  • Cell Proliferation*
  • Female
  • Fibroblasts* / metabolism
  • Fibroblasts* / pathology
  • Humans
  • Male
  • Metaplasia* / pathology
  • Mice
  • Middle Aged
  • Organoids / metabolism
  • Organoids / pathology
  • Salivary Glands* / metabolism
  • Salivary Glands* / pathology
  • Sialometaplasia, Necrotizing* / genetics
  • Sialometaplasia, Necrotizing* / metabolism
  • Sialometaplasia, Necrotizing* / pathology
  • Transforming Growth Factor beta3* / genetics
  • Transforming Growth Factor beta3* / metabolism

Substances

  • TGFB3 protein, human
  • Transforming Growth Factor beta3
  • Tgfb3 protein, mouse