β-Adrenergic signaling induces Notch-mediated salivary gland progenitor cell control

X. Wang, P. Serrano Martinez, J. H. Terpstra, A. Shaalan, G. B. Proctor, F. K.L. Spijkervet, A. Vissink, H. Bootsma, F. G.M. Kroese, R. P. Coppes, S. Pringle*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

5 Citations (Scopus)

Abstract

β-Adrenergic signaling blockade is a mainstay of hypertension management. One percent of patients taking β-blockers develop reduced salivary gland (SG) function. Here we investigate the role of SG progenitor cells in β-blocker-induced hyposalivation, using human SG organoid cultures (SGOs). Compared with control SGs, initial low SG progenitor cell yield from patients taking β-blockers was observed. When passaged, these SGOs recovered self-renewal and upregulated Notch pathway expression. Notch signaling was downregulated in situ in β-adrenergic receptor-expressing luminal intercalated duct (ID) cells of patients taking β-blockers. Control SGOs treated with β-adrenergic agonist isoproterenol demonstrated increased proportion of luminal ID SGO cells with active Notch signaling. Control SGOs exposed to isoproterenol differentiated into more mature SGOs (mSGOs) expressing markers of acinar cells. We propose that β-blocker-induced Notch signaling reduction in luminal ID cells hampers their ability to proliferate and differentiate into acinar cells, inducing a persistent hyposalivation in some patients taking β-blocking medication.

Original languageEnglish
Pages (from-to)2813-2824
Number of pages12
JournalStem cell reports
Volume16
Issue number11
Early online date5 Oct 2021
DOIs
Publication statusPublished - 21 Oct 2021

Keywords

  • hyposalivation
  • progenitor cells
  • salivary gland
  • β-adrenergic signaling
  • β-blockers

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