RRC ID 78029
Author Tokumasu R, Yasuhara R, Kang S, Funatsu T, Mishima K.
Title Transcription factor FoxO1 regulates myoepithelial cell diversity and growth.
Journal Sci Rep
Abstract Salivary gland myoepithelial cells regulate saliva secretion and have been implicated in the histological diversity of salivary gland tumors. However, detailed functional analysis of myoepithelial cells has not been determined owing to the few of the specific marker to isolate them. We isolated myoepithelial cells from the submandibular glands of adult mice using the epithelial marker EpCAM and the cell adhesion molecule CD49f as indicators and found predominant expression of the transcription factor FoxO1 in these cells. RNA-sequence analysis revealed that the expression of cell cycle regulators was negatively regulated in FoxO1-overexpressing cells. Chromatin immunoprecipitation analysis showed that FoxO1 bound to the p21/p27 promoter DNA, indicating that FoxO1 suppresses cell proliferation through these factors. In addition, FoxO1 induced the expression of ectodysplasin A (Eda) and its receptor Eda2r, which are known to be associated with X-linked hypohidrotic ectodermal dysplasia and are involved in salivary gland development in myoepithelial cells. FoxO1 inhibitors suppressed Eda/Eda2r expression and salivary gland development in primordial organ cultures after mesenchymal removal. Although mesenchymal cells are considered a source of Eda, myoepithelial cells might be one of the resources of Eda. These results suggest that FoxO1 regulates myoepithelial cell proliferation and Eda secretion during salivary gland development in myoepithelial cells.
Volume 14(1)
Pages 1069
Published 2024-1-11
DOI 10.1038/s41598-024-51619-1
PII 10.1038/s41598-024-51619-1
PMID 38212454
PMC PMC10784559
MeSH Animals Ectodysplasins / genetics Epithelial Cells / metabolism Mice Receptors, Tumor Necrosis Factor / metabolism Salivary Gland Neoplasms* / metabolism Submandibular Gland / metabolism Transcription Factors* / metabolism Xedar Receptor / metabolism
IF 3.998
Mice RBRC01361