局部损伤的上皮屏障功能可导致原发性SJ干燥综合征样自身免疫性疾病。
发表者：杨麟
日期：2015-03-04
浏览次数：159
评论次数：0
摘要：原发性干燥综合征（PSS）是一种慢性自身免疫性疾病，主要累及泪腺和唾液腺，也能影响肺，肾，皮肤，甲状腺。像大多数风湿性疾病一样，PSS缺乏一个单一的区别性特征或诊断测试方法，因此其诊断必须要结合临床和实验室检查结果，包括眼部和口腔症状，唾液腺淋巴细胞浸润，以及自身抗体的存在。上皮细胞的遗传缺陷已经证明和自身免疫性疾病有关。在本研究中，研究者在小鼠模型中进一步研究了上皮屏障功能受损在PSS的发生中所起的作用，并研究了上皮屏障功能和间质蛋白酶表达之间的关系。该研究采用了两种不同的方法降低了小鼠模型中间质蛋白酶表达，导致上皮屏障功能下降，进一步检测了小鼠分泌上皮功能、泪腺和唾液腺功能，淋巴细胞浸润，血清抗Ro/SSA，抗La/SSB和抗核抗体的产生。同时，测定了唾液腺的免疫激活和调节，屏障功能以及紧密连接蛋白的功能。比较了PSS患者和健康志愿者小唾液腺matriptase的表达。结果显示在小鼠模型中观察到类似干燥综合征的产生。表型变化包括外分泌腺功能障碍，淋巴细胞浸润，干燥综合征特异性自身抗体的生产，和免疫系统的活化。唾液腺的分析表明，电位跨上皮层损失以及紧密连接蛋白的分布改变。此外，pSS患者唾液腺与健康志愿者相比，间质蛋白酶基因表达显著降低。该研究结果表明，局部损伤的上皮屏障功能可导致原发性SJ干燥综合征样自身免疫性疾病。
附原文：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 dysfunction in the absence of inflammation while systemic deletion can induce a primary Sjögren's syndrome like phenotype with autoimmunity and loss of gland function.
引自：Yin H, Kosa P, Liu X, Swaim WD, Lai Z, Cabrera-Perez J, Di Pasquale G, Ambudkar IS, Bugge TH, Chiorini JA.Matriptase Deletion Initiates a Sjögren's Syndrome-Like Disease in Mice.PLoS One. 2014 Feb 13;9(2):e82852. （注：干燥综合症病人或亲属可加QQ群交流，群号： 118194945 ，本网站站长私人微信号： ssgzz88 ）
附原文：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 dysfunction in the absence of inflammation while systemic deletion can induce a primary Sjögren's syndrome like phenotype with autoimmunity and loss of gland function.
引自：Yin H, Kosa P, Liu X, Swaim WD, Lai Z, Cabrera-Perez J, Di Pasquale G, Ambudkar IS, Bugge TH, Chiorini JA.Matriptase Deletion Initiates a Sjögren's Syndrome-Like Disease in Mice.PLoS One. 2014 Feb 13;9(2):e82852. （注：干燥综合症病人或亲属可加QQ群交流，群号： 118194945 ，本网站站长私人微信号： ssgzz88 ）