Insights into the molecular mechanism of Sjogren's syndrome
Langara, Hans A.
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Sjogren’s syndrome (SS) is a chronic autoimmune disease, that affects primarily salivary and lacrimal glands, leading to increased morbidity. Recent studies indicate that loss of salivary gland function is associated with defective cell polarity, lymphocytic infiltration and fibrosis. Our previous studies showed that deregulation of E-cadherin-mediated adhesion was associated with nuclear localization of YAP and suggested that the latter may be a key event in SS. In this study, our goal was to align altered morphological features in SS with cell polarity regulators. Specifically, we focused on the Par complex, known to play an important role in epithelial polarity, as well as components of tight junctions (TJs), ZO-1 and JAM-1, and compared them to changes in their expression and localization with markers of fibrosis, vimentin and α-smooth muscle actin (α-SMA). Using immunofluorescence staining and confocal microscopy we examined expression levels of YAP, Par3, ZO-1, JAM-1, vimentin, and α-SMA, and correlated them with a ductal differentiation marker K7 and a marker for lymphocytic infiltration, CD45+. Our results showed reduced levels of Par3, ZO-1 and JAM-1, in tissues from SS patients that were associated with increased nuclear localization of YAP. Collectively, these studies suggest that cell polarity cues are critical for normal function of salivary glands and that their deregulation is likely to be the underlying basis of at least a subset of SS patients. These findings will further contribute to a better understanding of the molecular basis of SS and will serve in improved diagnosis and future therapeutic intervention.