Inhibition of bone morphogenetic protein 6 receptors ameliorates Sjögren’s syndrome in mice
dc.contributor.author | Yin, Hongen | |
dc.contributor.author | Kalra, Lovika | |
dc.contributor.author | Lai, Zhennan | |
dc.contributor.author | Diniz, Maria Cambraia Guimaro | |
dc.contributor.author | Aber, Lauren | |
dc.contributor.author | Warner, Blake M. | |
dc.contributor.author | Michael, Drew | |
dc.contributor.author | Zhang, Nan | |
dc.contributor.author | Cabrera-Perez, Javier | |
dc.contributor.author | Karim, Arif | |
dc.contributor.author | Swaim, William D. | |
dc.contributor.author | Afione, Sandra | |
dc.contributor.author | Voigt, Alexandria | |
dc.contributor.author | Nguyen, Cuong Q. | |
dc.contributor.author | Yu, Paul B. | |
dc.contributor.author | Bloch , Donald B. | |
dc.contributor.author | Chiorini, John A. | |
dc.date.accessioned | 2022-10-31T14:59:32Z | |
dc.date.available | 2022-10-31T14:59:32Z | |
dc.date.issued | 2020-02-19 | |
dc.description.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. | en_US |
dc.description.sponsorship | Tis study was supported by an NIDCR, NIH intramural research grant to JAC (1ZIADE000695). PSS patients’ data and specimens used in this study were obtained from the Sjögren’s International Collaborative Clinical Alliance (SICCA) Biorepository, funded under contract #HHSN26S201300057C by the NIDCR. Tis manuscript/ presentation was prepared using a publicly available SICCA data set and does not necessarily refect the opinions or views of the SICCA investigators, the NIH or the NIDCR. Te authors appreciate Drs. Caroline Shiboski and Steven Shiboski’s useful advice in the study design for the pSS patient investigation, and Ms. Annie Chou, Ms. Danielle Drury and Ms. Yvonne De Souza’s help in organizing and shipping the specimens for this study. Te authors would like to thank the staf of the NIDCR Sjögren’s Syndrome Clinic for providing salivary gland tissue from healthy volunteers for this study. Finally, the authors would like to thank Dr. Peter Burbelo for critical discussions and the NIH Fellows Editorial Board for editorial assistance. | en_US |
dc.description.uri | https://www.nature.com/articles/s41598-020-59443-z | en_US |
dc.format.extent | 13 pages | en_US |
dc.genre | journal articles | en_US |
dc.identifier | doi:10.13016/m2fyvp-oxrk | |
dc.identifier.citation | 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 | en_US |
dc.identifier.uri | https://doi.org/10.1038/s41598-020-59443-z | |
dc.identifier.uri | http://hdl.handle.net/11603/26242 | |
dc.language.iso | en_US | en_US |
dc.publisher | Nature | en_US |
dc.relation.isAvailableAt | The University of Maryland, Baltimore County (UMBC) | |
dc.relation.ispartof | UMBC Office of the Dean of the College of Natural and Mathematical Sciences | |
dc.relation.ispartof | UMBC Faculty Collection | |
dc.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. | en_US |
dc.rights | Public Domain Mark 1.0 | * |
dc.rights.uri | http://creativecommons.org/publicdomain/mark/1.0/ | * |
dc.title | Inhibition of bone morphogenetic protein 6 receptors ameliorates Sjögren’s syndrome in mice | en_US |
dc.type | Text | en_US |
dcterms.creator | https://orcid.org/0000-0002-2633-9710 | en_US |
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