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TAZ inhibits acinar cell differentiation but promotes immature ductal cell proliferation in adult mouse salivary glands
- Source :
- Genes to Cells. 26:714-726
- Publication Year :
- 2021
- Publisher :
- Wiley, 2021.
-
Abstract
- There are currently no treatments for salivary gland diseases, making it vital to understand signaling mechanisms operating in acinar and ductal cells so as to develop regenerative therapies. To date, little work has focused on elucidating the signaling cascades controlling the differentiation of these cell types in adult mammals. To analyze the function of the Hippo-TAZ/YAP1 pathway in adult mouse salivary glands, we generated adMOB1DKO mice in which both MOB1A and MOB1B were TAM-inducibly deleted when the animals were adults. Three weeks after TAM treatment, adMOB1DKO mice exhibited smaller submandibular glands (SMGs) than controls with a decreased number of acinar cells and an increased number of immature dysplastic ductal cells. The mutants suffered from reduced saliva production accompanied by mild inflammatory cell infiltration and fibrosis in SMGs, similar to the Sjogren's syndrome. MOB1-deficient acinar cells showed normal proliferation and apoptosis but decreased differentiation, leading to an increase in acinar/ductal bilineage progenitor cells. These changes were TAZ-dependent but YAP1-independent. Biochemically, MOB1-deficient salivary epithelial cells showed activation of the TAZ/YAP1 and β-catenin in ductal cells, but reduced SOX2 and SOX10 expression in acinar cells. Thus, Hippo-TAZ signaling is critical for proper ductal and acinar cell differentiation and function in adult mice.
- Subjects :
- TAZ
Cell type
acinar cells
Ductal cells
Apoptosis
salivary gland
Biology
Salivary Glands
Mice
stomatognathic system
SOX2
Genetics
medicine
Animals
Progenitor cell
Cells, Cultured
beta Catenin
Adaptor Proteins, Signal Transducing
Cell Proliferation
Salivary gland
Cell growth
SOXB1 Transcription Factors
Intracellular Signaling Peptides and Proteins
Cell Differentiation
Cell Biology
MOB1
Mice, Inbred C57BL
ductal cells
medicine.anatomical_structure
Salivary Gland Diseases
Cancer research
hippo
Subjects
Details
- ISSN :
- 13652443 and 13569597
- Volume :
- 26
- Database :
- OpenAIRE
- Journal :
- Genes to Cells
- Accession number :
- edsair.doi.dedup.....b839e584d3956b92d236a82dc6e70681