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Up-regulation of Store-operated Ca2+ Entry and Nuclear Factor of Activated T Cells Promote the Acinar Phenotype of the Primary Human Salivary Gland Cells.
Jang, Shyh-Ing; Ong, Hwei Ling; Liu, Xibao; Alevizos, Ilias; Ambudkar, Indu S.
Affiliation
  • Jang SI; Sjögren's Syndrome and Salivary Gland Dysfunction Unit, Molecular Physiology and Therapeutics Branch, NIDCR/National Institutes of Health, Bethesda, Maryland 20892.
  • Ong HL; From the Secretory and Physiology Section and.
  • Liu X; From the Secretory and Physiology Section and.
  • Alevizos I; Sjögren's Syndrome and Salivary Gland Dysfunction Unit, Molecular Physiology and Therapeutics Branch, NIDCR/National Institutes of Health, Bethesda, Maryland 20892 alevizosi@nidcr.nih.gov.
  • Ambudkar IS; From the Secretory and Physiology Section and indu.ambudkar@nih.gov.
J Biol Chem ; 291(16): 8709-20, 2016 Apr 15.
Article in En | MEDLINE | ID: mdl-26903518
The signaling pathways involved in the generation and maintenance of exocrine gland acinar cells have not yet been established. Primary human salivary gland epithelial cells, derived from salivary gland biopsies, acquired an acinar-like phenotype when the [Ca(2+)] in the serum-free medium (keratinocyte growth medium, KGM) was increased from 0.05 mm (KGM-L) to 1.2 mm (KGM-H). Here we examined the mechanism underlying this Ca(2+)-dependent generation of the acinar cell phenotype. Compared with cells in KGM-L, those in KGM-H display enhancement of Orai1, STIM1, STIM2, and nuclear factor of activated T cells 1 (NFAT1) expression together with an increase in store-operated Ca(2+) entry (SOCE), SOCE-dependent nuclear translocation of pGFP-NFAT1, and NFAT-dependent but not NFκB-dependent gene expression. Importantly, AQP5, an acinar-specific protein critical for function, is up-regulated in KGM-H via SOCE/NFAT-dependent gene expression. We identified critical NFAT binding motifs in the AQP5 promoter that are involved in Ca(2+)-dependent up-regulation of AQP5. These important findings reveal that the Ca(2+)-induced switch of salivary epithelial cells to an acinar-like phenotype involves remodeling of SOCE and NFAT signaling, which together control the expression of proteins critically relevant for acinar cell function. Our data provide a novel strategy for generating and maintaining acinar cells in culture.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Salivary Glands / Up-Regulation / Calcium / Calcium Signaling / Epithelial Cells / NFATC Transcription Factors Type of study: Prognostic_studies Limits: Humans Language: En Journal: J Biol Chem Year: 2016 Document type: Article Country of publication:

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Salivary Glands / Up-Regulation / Calcium / Calcium Signaling / Epithelial Cells / NFATC Transcription Factors Type of study: Prognostic_studies Limits: Humans Language: En Journal: J Biol Chem Year: 2016 Document type: Article Country of publication: