ß-Adrenergic signaling induces Notch-mediated salivary gland progenitor cell control.
Stem Cell Reports
; 16(11): 2813-2824, 2021 11 09.
Article
in En
| MEDLINE
| ID: mdl-34678204
ABSTRACT
ß-Adrenergic signaling blockade is a mainstay of hypertension management. One percent of patients taking ß-blockers develop reduced salivary gland (SG) function. Here we investigate the role of SG progenitor cells in ß-blocker-induced hyposalivation, using human SG organoid cultures (SGOs). Compared with control SGs, initial low SG progenitor cell yield from patients taking ß-blockers was observed. When passaged, these SGOs recovered self-renewal and upregulated Notch pathway expression. Notch signaling was downregulated in situ in ß-adrenergic receptor-expressing luminal intercalated duct (ID) cells of patients taking ß-blockers. Control SGOs treated with ß-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 ß-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 ß-blocking medication.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Salivary Glands
/
Stem Cells
/
Signal Transduction
/
Receptors, Adrenergic
/
Receptors, Notch
Limits:
Humans
Language:
En
Journal:
Stem Cell Reports
Year:
2021
Document type:
Article
Affiliation country:
Países Bajos
Publication country:
EEUU
/
ESTADOS UNIDOS
/
ESTADOS UNIDOS DA AMERICA
/
EUA
/
UNITED STATES
/
UNITED STATES OF AMERICA
/
US
/
USA