Objective: To identify cell biological defects in SS, we assessed the localization of TAZ, a transcriptional coactivator with key roles in cell polarity and in mechanosensing the extracellular matrix (ECM) stiffness. We aligned changes in TAZ localization with those in fibronectin, a component of the ECM, and in matrix metalloproteinase 9 (MMP9) that functions in the remodeling of the ECM.
Method: Formalin-fixed and paraffin-embedded minor labial salivary gland SS specimens and non-compatible controls were stained for ZO-1, E-cadherin, β-catenin, MMP-9, fibronectin and TAZ using indirect immunofluorescence and analyzed by confocal microscopy.
Result: In a subset of SS specimens, E-cadherin, β-catenin and ZO-1 exhibited disrupted staining. Fibronectin organization was less prominent, displaying a punctate pattern surrounding the acini. In contrast, MMP-9 was more pronounced in the basal regions of acini and colocalized with nuclei. Importantly, in SS specimens TAZ was less localized to cell-cell borders, exhibiting more nuclear and cytoplasmic staining, suggesting that the observed changes in the ECM and polarity were linked to its altered distribution.
Conclusion: Our studies show for the first time that structural defects in a subset of SS phenotypes may be associated with changes in the distribution of TAZ, a regulator of cell polarity and a sensor of mechanical cues.
Keywords: Growth & development, Salivary dysfunction, Salivary glands and TAZ