Inhibition of bone morphogenetic protein 6 receptors ameliorates Sjögren’s syndrome in mice

Thumbnail Image

Files

s41598-020-59443-z.pdf (1.77 MB)
41598_2020_59443_MOESM1_ESM.pdf (859.78 KB)

Links to Files

https://www.nature.com/articles/s41598-020-59443-z

Permanent Link

https://doi.org/10.1038/s41598-020-59443-z
 http://hdl.handle.net/11603/26242

Collections

UMBC Office of the Dean of the College of Natural and Mathematical Sciences
UMBC Faculty Collection

Author/Creator

Author/Creator ORCID

https://orcid.org/0000-0002-2633-9710

Date

2020-02-19

Type of Work

journal articles
Text

Department

Program

Citation of Original Publication

Yin, H., Kalra, L., Lai, Z. et al. Inhibition of bone morphogenetic protein 6 receptors ameliorates Sjögren’s syndrome in mice. Sci Rep 10, 2967 (2020). https://doi.org/10.1038/s41598-020-59443-z

Rights

This work was written as part of one of the author's official duties as an Employee of the United States Government and is therefore a work of the United States Government. In accordance with 17 U.S.C. 105, no copyright protection is available for such works under U.S. Law.
Public Domain Mark 1.0

Subjects

Abstract

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 efcacy 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 fow 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 infammatory 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.