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MUC1/SEC和MUC1/Y的过表达与干燥综合征中的炎症相关。

MUC1/SEC and MUC1/Y overexpression is associated with inflammation in Sjögren's syndrome.

作者信息

Sung H H, Castro I, González S, Aguilera S, Smorodinsky N I, Quest Afg, Bahamondes V, Alliende C, Cortés J, Molina C, Urzúa U, Barrera M-J, Hermoso M, Herrera L, Leyton C, González M-J

机构信息

Instituto de Ciencias Biomédicas, Facultad de Medicina, Universidad de Chile, Santiago, Chile.

Facultad de Odontología, Universidad Mayor, Santiago, Chile.

出版信息

Oral Dis. 2015 Sep;21(6):730-8. doi: 10.1111/odi.12339. Epub 2015 Apr 6.

Abstract

OBJECTIVES

To evaluate the expression and localization of MUC1/SEC and MUC1/Y isoforms in labial salivary glands (LSG) from Sjögren's syndrome patients (SS patients), as well as their in vitro expression induced by cytokines.

SUBJECTS AND METHODS

Labial salivary gland from 27 primary SS patients and 22 non-SS sicca subjects were studied. Relative MUC1/SEC and MUC1/Y mRNA levels were determined by qPCR and protein levels by Western blotting. Induction of mucin mRNAs was assayed in vitro. Immunohistochemistry was used for localization.

RESULTS

Relative MUC1/SEC and MUC1/Y mRNA and protein levels were significantly higher in LSG from SS patients. These mRNAs were induced by cytokines. MUC1/SEC and MUC1/Y were detected in acini apical region of control LSGs, and significant cytoplasmic accumulation was observed in acini of SS patients. MUC1/Y localized in acinar nuclei and cytoplasm of inflammatory cells of LSG from SS patients. A strong positive correlation was observed between cellular MUC1/SEC levels and glandular function determined by scintigraphy.

CONCLUSIONS

We show for the first time that MUC1/SEC and MUC1/Y are expressed in LSG of both SS patients and non-SS sicca subjects. The observed overexpression and aberrant localization of MUC1/SEC and MUC1/Y and their induction by pro-inflammatory cytokines may favor the perpetuation of the inflammatory environment that disrupts the salivary glandular homeostasis in SS patients.

摘要

目的

评估MUC1/SEC和MUC1/Y亚型在干燥综合征(SS)患者唇腺(LSG)中的表达及定位,以及细胞因子对其体外表达的诱导作用。

对象与方法

研究了27例原发性SS患者和22例非SS口干受试者的唇腺。通过qPCR测定相对MUC1/SEC和MUC1/Y mRNA水平,通过蛋白质印迹法测定蛋白质水平。体外检测黏蛋白mRNA的诱导情况。采用免疫组织化学法进行定位。

结果

SS患者LSG中相对MUC1/SEC和MUC1/Y mRNA及蛋白质水平显著更高。这些mRNA由细胞因子诱导产生。在对照LSG的腺泡顶端区域检测到MUC1/SEC和MUC1/Y,在SS患者的腺泡中观察到明显的细胞质积聚。MUC1/Y定位于SS患者LSG炎症细胞的腺泡细胞核和细胞质中。细胞MUC1/SEC水平与闪烁扫描测定的腺体功能之间存在强正相关。

结论

我们首次表明MUC1/SEC和MUC1/Y在SS患者和非SS口干受试者的LSG中均有表达。观察到的MUC1/SEC和MUC1/Y的过表达、异常定位及其由促炎细胞因子诱导的情况,可能有利于维持破坏SS患者唾液腺内环境稳定的炎症环境。

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