@article{55f45bd79a1d4bfb9468598d3b4b0541,
title = "β-Adrenergic signaling induces Notch-mediated salivary gland progenitor cell control",
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.",
keywords = "hyposalivation, progenitor cells, salivary gland, β-adrenergic signaling, β-blockers",
author = "X. Wang and Martinez, {P. Serrano} and Terpstra, {J. H.} and A. Shaalan and Proctor, {G. B.} and Spijkervet, {F. K.L.} and A. Vissink and H. Bootsma and Kroese, {F. G.M.} and Coppes, {R. P.} and S. Pringle",
note = "Funding Information: We gratefully acknowledge the maxillofacial surgical teams at the University Medical Center Groningen (Prof. Max Witjes) and Medical Center Leeuwarden (Dr. Eric van der Meij, Dr. Christiaan Krabbe and Dr. Visscher) for their continuous collaboration and coordination of tissue collection. Financial support: this research was funded by a China Scholarship Council grant ( 201606220074 ), Dutch Arthritis Foundation Translational Research Grant ( T015-052 ), and a Dutch Arthritis Foundation Long Term Project Grant ( LLP-29 ). Funding Information: We gratefully acknowledge the maxillofacial surgical teams at the University Medical Center Groningen (Prof. Max Witjes) and Medical Center Leeuwarden (Dr. Eric van der Meij, Dr. Christiaan Krabbe and Dr. Visscher) for their continuous collaboration and coordination of tissue collection. Financial support: this research was funded by a China Scholarship Council grant (201606220074), Dutch Arthritis Foundation Translational Research Grant (T015-052), and a Dutch Arthritis Foundation Long Term Project Grant (LLP-29). Publisher Copyright: {\textcopyright} 2021 The Authors",
year = "2021",
month = oct,
day = "21",
doi = "10.1016/j.stemcr.2021.09.015",
language = "English",
volume = "16",
pages = "2813--2824",
journal = "Stem cell reports",
issn = "2213-6711",
publisher = "CELL PRESS",
number = "11",
}