Extracellular matrix turnover in salivary gland disorders and regenerative therapies: Obstacles and opportunities

Milos Marinkovic, Olivia N. Tran, Hanzhou Wang, Parveez Abdul-Azees, David D. Dean, Xiao Dong Chen, Chih Ko Yeh

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Salivary gland (SG) extracellular matrix (ECM) has a major influence on tissue development, homeostasis, and tissue regeneration after injury. During aging, disease, and physical insult, normal remodeling of the SG microenvironment (i.e. ECM) becomes dysregulated, leading to alterations in matrix composition which disrupt tissue architecture/structure, alter cell activity, and negatively impact gland function. Matrix metalloproteinases (MMPs) are a large and diverse family of metalloendopeptidases which play a major role in matrix degradation and are intimately involved in regulating development and cell function; dysregulation of these enzymes leads to the production of a fibrotic matrix. In the SG this altered fibrotic ECM (or cell microenvironment) negatively impacts normal cell function and the effectiveness of gene and stem cell therapies which serve as a foundation for many SG regenerative therapies. For this reason, prospective regenerative strategies should prioritize the maintenance and/or restoration of a healthy SG ECM. Mesenchymal stem cells (MSCs) have great potential for mitigating damage to the SG microenvironment by ameliorating inflammation, reducing fibrosis, and repairing the damaged milieu of extracellular regulatory cues, including the matrix. This review addresses our current understanding of the impact of aging and disease on the SG microenvironment and suggests critical deficiencies and opportunities in ECM-targeted therapeutic interventions.

Original languageEnglish (US)
Pages (from-to)693-703
Number of pages11
JournalJournal of Oral Biology and Craniofacial Research
Volume13
Issue number6
DOIs
StatePublished - Nov 1 2023

Keywords

  • Aging
  • Extracellular matrix
  • Fibrosis
  • Matrix metalloproteinases
  • Salivary gland
  • Tissue remodeling

ASJC Scopus subject areas

  • General Dentistry
  • Otorhinolaryngology

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