beta-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*

*Bijbehorende auteur voor dit werk

OnderzoeksoutputAcademicpeer review

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beta-Adrenergic signaling blockade is a mainstay of hypertension management. One percent of patients taking beta-blockers develop reduced salivary gland (SG) function. Here we investigate the role of SG progenitor cells in beta-blocker-induced hyposalivation, using human SG organoid cultures (SGOs). Compared with control SGs, initial low SG progenitor cell yield from patients taking beta-blockers was observed. When passaged, these SGOs recovered self-renewal and upregulated Notch pathway expression. Notch signaling was downregulated in situ in beta-adrenergic receptor-expressing luminal intercalated duct (ID) cells of patients taking beta-blockers. Control SGOs treated with beta-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 beta-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 beta-blocking medication.

Originele taal-2English
Pagina's (van-tot)2813-2824
Aantal pagina's12
TijdschriftStem Cell Reports
Nummer van het tijdschrift11
StatusPublished - 9-nov-2021

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