GPR55 controls functional differentiation of self-renewing epithelial progenitors for salivation.
Adult
Adult Stem Cells
/ drug effects
Aged
Aged, 80 and over
Animals
Cannabinoid Receptor Agonists
/ pharmacology
Cannabinoid Receptor Antagonists
/ pharmacology
Carcinoma, Mucoepidermoid
/ pathology
Cell Differentiation
/ drug effects
Cell Self Renewal
/ drug effects
Down-Regulation
Epithelial Cells
/ drug effects
Female
Glycoproteins
/ metabolism
Humans
Male
Mice
Mice, Knockout
Middle Aged
Receptors, Cannabinoid
/ genetics
Saliva
/ chemistry
Salivary Gland Neoplasms
/ pathology
Salivation
/ drug effects
Submandibular Gland
/ drug effects
Endocrinology
G-protein coupled receptors
Gastroenterology
Journal
JCI insight
ISSN: 2379-3708
Titre abrégé: JCI Insight
Pays: United States
ID NLM: 101676073
Informations de publication
Date de publication:
21 02 2019
21 02 2019
Historique:
received:
21
06
2018
accepted:
11
01
2019
entrez:
5
3
2019
pubmed:
5
3
2019
medline:
12
5
2020
Statut:
epublish
Résumé
GPR55, a lipid-sensing receptor, is implicated in cell cycle control, malignant cell mobilization, and tissue invasion in cancer. However, a physiological role for GPR55 is virtually unknown for any tissue type. Here, we localize GPR55 to self-renewing ductal epithelial cells and their terminally differentiated progeny in both human and mouse salivary glands. Moreover, we find GPR55 expression downregulated in salivary gland mucoepidermoid carcinomas and GPR55 reinstatement by antitumor irradiation, suggesting that GPR55 controls renegade proliferation. Indeed, GPR55 antagonism increases cell proliferation and function determination in quasiphysiological systems. In addition, Gpr55-/- mice present ~50% enlarged submandibular glands with many more granulated ducts, as well as disordered endoplasmic reticuli and with glycoprotein content. Next, we hypothesized that GPR55 could also modulate salivation and glycoprotein content by entraining differentiated excretory progeny. Accordingly, GPR55 activation facilitated glycoprotein release by itself, inducing low-amplitude Ca2+ oscillations, as well as enhancing acetylcholine-induced Ca2+ responses. Topical application of GPR55 agonists, which are ineffective in Gpr55-/- mice, into adult rodent submandibular glands increased salivation and saliva glycoprotein content. Overall, we propose that GPR55 signaling in epithelial cells ensures both the life-long renewal of ductal cells and the continuous availability of saliva and glycoproteins for oral health and food intake.
Identifiants
pubmed: 30830860
pii: 122947
doi: 10.1172/jci.insight.122947
pmc: PMC6478415
doi:
pii:
Substances chimiques
Cannabinoid Receptor Agonists
0
Cannabinoid Receptor Antagonists
0
GPR55 protein, human
0
GPR55 protein, mouse
0
Glycoproteins
0
Receptors, Cannabinoid
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
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