Inhibition of bone morphogenetic protein 6 receptors ameliorates Sjögren's syndrome in mice.
Activin Receptors, Type I
/ antagonists & inhibitors
Adult
Aged
Animals
Bone Morphogenetic Protein 6
/ analysis
Cell Line
Female
Healthy Volunteers
Humans
Male
Mice
Mice, Transgenic
Middle Aged
Phosphorylation
/ drug effects
Pyrazoles
/ administration & dosage
Pyrimidines
/ administration & dosage
Quinolines
/ administration & dosage
Recovery of Function
/ drug effects
Saliva
/ immunology
Salivary Glands
/ drug effects
Signal Transduction
/ drug effects
Sjogren's Syndrome
/ drug therapy
Smad Proteins, Receptor-Regulated
/ metabolism
Young Adult
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
19 02 2020
19 02 2020
Historique:
received:
15
07
2019
accepted:
16
01
2020
entrez:
21
2
2020
pubmed:
23
2
2020
medline:
21
11
2020
Statut:
epublish
Résumé
Primary Sjögren's syndrome (pSS) is a chronic autoimmune disease, with only palliative treatments available. Recent work has suggested that increased bone morphogenetic protein 6 (BMP6) expression could alter cell signaling in the salivary gland (SG) and result in the associated salivary hypofunction. We examined the prevalence of elevated BMP6 expression in a large cohort of pSS patients and tested the therapeutic efficacy of BMP signaling inhibitors in two pSS animal models. Increased BMP6 expression was found in the SGs of 54% of pSS patients, and this increased expression was correlated with low unstimulated whole saliva flow rate. In mouse models of SS, inhibition of BMP6 signaling reduced phosphorylation of SMAD1/5/8 in the mouse submandibular glands, and led to a recovery of SG function and a decrease in inflammatory markers in the mice. The recovery of SG function after inhibition of BMP6 signaling suggests cellular plasticity within the salivary gland and a possibility for therapeutic intervention that can reverse the loss of function in pSS.
Identifiants
pubmed: 32076051
doi: 10.1038/s41598-020-59443-z
pii: 10.1038/s41598-020-59443-z
pmc: PMC7031521
doi:
Substances chimiques
BMP6 protein, human
0
Bmp6 protein, mouse
0
Bone Morphogenetic Protein 6
0
LDN 193189
0
LDN-212854
0
Pyrazoles
0
Pyrimidines
0
Quinolines
0
Smad Proteins, Receptor-Regulated
0
Activin Receptors, Type I
EC 2.7.11.30
Types de publication
Journal Article
Observational Study
Research Support, N.I.H., Extramural
Research Support, N.I.H., Intramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
2967Subventions
Organisme : NIAMS NIH HHS
ID : R01 AR057374
Pays : United States
Organisme : Intramural NIH HHS
ID : ZIA DE000695
Pays : United States
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