Details

Autor(en) / Beteiligte

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

Titel

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

Ist Teil von

• Stem cell reports, 2021-11, Vol.16 (11), p.2813-2824

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2021

Quelle

MEDLINE

Beschreibungen/Notizen

• 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. [Display omitted] •SG organoids from patients taking β-adrenergic blockers show low yield•Notch signaling in parotid SG luminal ID cells decreases with β-blocker use•β-Adrenergic stimulation induces proliferation of parotid SG luminal ID cells•β-Adrenergic-induced Notch activity stimulates SGO differentiation into mSGOs Loss of salivary gland function is commonly experienced as a side effect of β-adrenergic signal blocking medication (β-blockers), used for treatment of hypertension. In this article, Wang et al. show that β-adrenergic signaling controls proliferation and differentiation of human parotid salivary gland progenitor cells, via activation of the Notch pathway. Blockade of this signal by use of β-blockers may explain persistent hyposalivation in these patients.