Longitudinal analysis of tear cathepsin S activity levels in male non-obese diabetic mice suggests its potential as an early stage biomarker of Sjögren's Syndrome

对雄性非肥胖糖尿病小鼠泪液蛋白酶 S 活性水平的纵向分析表明其可能成为干燥综合征的早期生物标志物

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作者:Srikanth R Janga, Mihir Shah, Yaping Ju, Zhen Meng, Maria C Edman, Sarah F Hamm-Alvarez

Conclusion

Tear CTSS activity is elevated with other early disease indicators, suggesting potential as an early stage biomarker for SS.

Methods

CTSS activity was measured in tears and lacrimal glands (LG) from male 1-6 month (M) NOD and 1 and 6 M BALB/c mice. Lymphocytic infiltration was quantified by histopathology, while disease-related proteins (Rab3D, CTSS, collagen 1) were quantified using q-PCR and immunofluorescence.

Objective

To evaluate longitudinal expression of tear and tissue CTSS activity relative to other disease indicators in Non-Obese Diabetic (NOD) mice.

Results

In NOD LG, lymphocytic infiltration was noted by 2 M and established by 3 M (p < 0.01). IFN-ɣ, TNF-α, and MHC II expression were increased by 2 M (p < 0.01). Tear CTSS activity was significantly elevated at 2 M (p < 0.001) to a maximum of 10.1-fold by 6 M (p < 0.001). CTSS activity in LG lysates was significantly elevated by 2 M (p < 0.001) to a maximum of 14-fold by 3 M (p < 0.001). CTSS and Rab3D immunofluorescence were significantly increased and decreased maximally in LG acini by 3 M and 2 M, respectively. Comparable changes were not detected between 1 and 6 M BALB/c mouse LG, although Collagen 1 was decreased by 6 M in LG of both strains.

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