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Matriptase deletion initiates a Sjögren's syndrome-like disease in mice.
PLoS One. 2014; 9(2):e82852.Plos

Abstract

OBJECTIVE

The objective of this study was to determine the effect of epithelial barrier disruption, caused by deficiency of the membrane-anchored serine protease, matriptase, on salivary gland function and the induction of autoimmunity in an animal model.

METHODS

Embryonic and acute ablation of matriptase expression in the salivary glands of mice was induced, leading to decreased epithelial barrier function. Mice were characterized for secretory epithelial function and the induction of autoimmunity including salivary and lacrimal gland dysfunction, lymphocytic infiltration, serum anti-Ro/SSA, anti-La/SSB and antinuclear antibodies. Salivary glands immune activation/regulation, barrier function as well as tight junction proteins expression also were determined. Expression of matriptase in minor salivary gland biopsies was compared among pSS patients and healthy volunteers.

RESULTS

Embryonic ablation of matriptase expression in mice resulted in the loss of secretory epithelial cell function and the induction of autoimmunity similar to that observed in primary Sjögren's syndrome. Phenotypic changes included exocrine gland dysfunction, lymphocytic infiltrates, production of Sjögren's syndrome-specific autoantibodies, and overall activation of the immune system. Acute ablation of matriptase expression resulted in significant salivary gland dysfunction in the absence of overt immune activation. Analysis of the salivary glands indicates a loss of electrical potential across the epithelial layer as well as altered distribution of a tight junction protein. Moreover, a significant decrease in matriptase gene expression was detected in the minor salivary glands of pSS patients compared with healthy volunteers.

CONCLUSIONS

Our findings demonstrate that local impairment of epithelial barrier function can lead to loss of exocrine gland function [corrected] in the absence of inflammation while systemic deletion can induce a primary Sjögren's syndrome like phenotype with autoimmunity and loss of gland function.

Authors+Show Affiliations

Molecular Physiology and Therapeutics Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, Maryland, United States of America.Oral and Pharyngeal Cancer Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, Maryland, United States of America.Molecular Physiology and Therapeutics Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, Maryland, United States of America.Molecular Physiology and Therapeutics Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, Maryland, United States of America.Molecular Physiology and Therapeutics Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, Maryland, United States of America.Molecular Physiology and Therapeutics Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, Maryland, United States of America.Molecular Physiology and Therapeutics Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, Maryland, United States of America.Molecular Physiology and Therapeutics Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, Maryland, United States of America.Oral and Pharyngeal Cancer Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, Maryland, United States of America.Molecular Physiology and Therapeutics Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, Maryland, United States of America.

Pub Type(s)

Journal Article
Research Support, N.I.H., Intramural

Language

eng

PubMed ID

24551030

Citation

Yin, Hongen, et al. "Matriptase Deletion Initiates a Sjögren's Syndrome-like Disease in Mice." PloS One, vol. 9, no. 2, 2014, pp. e82852.
Yin H, Kosa P, Liu X, et al. Matriptase deletion initiates a Sjögren's syndrome-like disease in mice. PLoS One. 2014;9(2):e82852.
Yin, H., Kosa, P., Liu, X., Swaim, W. D., Lai, Z., Cabrera-Perez, J., Di Pasquale, G., Ambudkar, I. S., Bugge, T. H., & Chiorini, J. A. (2014). Matriptase deletion initiates a Sjögren's syndrome-like disease in mice. PloS One, 9(2), e82852. https://doi.org/10.1371/journal.pone.0082852
Yin H, et al. Matriptase Deletion Initiates a Sjögren's Syndrome-like Disease in Mice. PLoS One. 2014;9(2):e82852. PubMed PMID: 24551030.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Matriptase deletion initiates a Sjögren's syndrome-like disease in mice. AU - Yin,Hongen, AU - Kosa,Peter, AU - Liu,Xibao, AU - Swaim,William D, AU - Lai,Zhennan, AU - Cabrera-Perez,Javier, AU - Di Pasquale,Giovanni, AU - Ambudkar,Indu S, AU - Bugge,Thomas H, AU - Chiorini,John A, Y1 - 2014/02/13/ PY - 2013/04/22/received PY - 2013/10/28/accepted PY - 2014/2/20/entrez PY - 2014/2/20/pubmed PY - 2014/10/15/medline SP - e82852 EP - e82852 JF - PloS one JO - PLoS One VL - 9 IS - 2 N2 - OBJECTIVE: The objective of this study was to determine the effect of epithelial barrier disruption, caused by deficiency of the membrane-anchored serine protease, matriptase, on salivary gland function and the induction of autoimmunity in an animal model. METHODS: Embryonic and acute ablation of matriptase expression in the salivary glands of mice was induced, leading to decreased epithelial barrier function. Mice were characterized for secretory epithelial function and the induction of autoimmunity including salivary and lacrimal gland dysfunction, lymphocytic infiltration, serum anti-Ro/SSA, anti-La/SSB and antinuclear antibodies. Salivary glands immune activation/regulation, barrier function as well as tight junction proteins expression also were determined. Expression of matriptase in minor salivary gland biopsies was compared among pSS patients and healthy volunteers. RESULTS: Embryonic ablation of matriptase expression in mice resulted in the loss of secretory epithelial cell function and the induction of autoimmunity similar to that observed in primary Sjögren's syndrome. Phenotypic changes included exocrine gland dysfunction, lymphocytic infiltrates, production of Sjögren's syndrome-specific autoantibodies, and overall activation of the immune system. Acute ablation of matriptase expression resulted in significant salivary gland dysfunction in the absence of overt immune activation. Analysis of the salivary glands indicates a loss of electrical potential across the epithelial layer as well as altered distribution of a tight junction protein. Moreover, a significant decrease in matriptase gene expression was detected in the minor salivary glands of pSS patients compared with healthy volunteers. CONCLUSIONS: Our findings demonstrate that local impairment of epithelial barrier function can lead to loss of exocrine gland function [corrected] in the absence of inflammation while systemic deletion can induce a primary Sjögren's syndrome like phenotype with autoimmunity and loss of gland function. SN - 1932-6203 UR - https://www.unboundmedicine.com/medline/citation/24551030/Matriptase_deletion_initiates_a_Sjögren's_syndrome_like_disease_in_mice_ L2 - https://dx.plos.org/10.1371/journal.pone.0082852 DB - PRIME DP - Unbound Medicine ER -