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K. Wu, S. Xu, X. Li, C.-Y. Chen, M. MacVeigh, S. Hamm-Alvarez; Alteration of Genes Regulating Protein Post-Translational Modification Revealed by Gene Expression Profiles in NOD Lacrimal Gland. Invest. Ophthalmol. Vis. Sci. 2007;48(13):1908.
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© ARVO (1962-2015); The Authors (2016-present)
Sjogren’s syndrome (SS) is a chronic autoimmune disease in which immune cells infiltrate and damage the lacrimal glands (LG) of patients. In the NOD mouse model which recapitulates many aspects of human SS, the massive immune cell infiltration into the male LG is detectable in mice aged 12 weeks or younger. Additional changes detected in the LG of this disease model concomitant with or prior to lymphocytic infiltration include acinar cell swelling and considerable loosening of connections between the adjacent acini. We utilized microarray analysis to explore the underlying changes in gene expression that might contribute to these changes.
We purified RNA from the LG of male NOD mice at 12 weeks in comparison to that in age- and gender-matched BALB/c mice and then characterized the gene expression profiles by ABI cDNA microarray.
The experiment detected eight sialyltransferases mRNAs in LG which included Siat4A, Siat4C, Siat6, Siat7A, Siat7B, Siat7C, Siat9 and Siat10. Among these mRNAs, three were differentially expressed including Siat7A, Siat7B and Siat10. Their relative quantities in NOD compared to the control group were 125.00, 0.21 and 10.03. The results were validated by real-time PCR as 123.83, 0.26 and 3.47, respectively. Results from real-time PCR also showed that the mRNA level of Siat7A in the LG of female NOD mice, which exhibit a lesser degree of SS-like changes, was also higher than the control BALB/c female, but to a lesser extent (26.80-fold). Siat7A is the glycosyltransferase responsible for the production of the biomarker, sialyl-Tn antigen, which is highly expressed in many types of cancers and linked to unfavorable prognosis. Overexpression of Siat7A is associated with altered cellular size and adhesive properties.
We propose that Siat7A, with other sialyltransferases, plays a critical role in cellular surface protein modifications in LG. The significant change in their activities may contribute to the pathogenesis of the SS-like disease in mice by altering the cell surface, thus impacting cell-cell interactions and modulating signaling between acinar cells and/or the signaling of acinar cells with other cell types in LG.
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