Activation of a Local Renin-angiotensin-system in the Salivary Glands of Non-obese Diabetic Mice

Objectives: Sjögren’s Syndrome (SjS), is an autoimmune disease characterized by lymphocytic infiltration and chronic inflammation of exocrine glands leading to loss of secretory function. There is a critical need to detect and monitor the disease early and develop targeted treatments to decrease inflammation and restore secretory function. Here, we explored whether saliva collected from a SjS-like disease mouse model before disease onset contains protein and peptide signatures that could inform on the molecular mechanisms leading to SjS-like hyposalivation.

Methods: We collected saliva from female mice (NOD, C57BL/6 and BALB/c strains) at seven weeks of age before the onset of salivary gland dysfunction in NOD-mice. We used liquid-chromatography tandem mass spectrometry (LC-MS/MS)-based workflows along with bioinformatic approaches to identify and quantify proteins and endogenous peptides.
Results: Consistent with hyposalivation as a sign of SjS-like salivary gland dysfunction, NOD mice displayed decreased salivary flow rates at seven weeks of age compared to the two control strains (C57BL/6 and BALB/c). Hierarchical clustering analysis of the relative peptide and protein abundance revealed that mice with identical genetic backgrounds shared very similar expression levels for endogenous peptides and proteins and that those profiles were distinct for each mouse strain. Renin, the initial enzyme of the namesake renin-angiotensin system, BPIFB1 (BPI fold-containing family B member 1) and angiotensin peptides were significantly elevated in saliva collected from NOD-mice compared to B6 and BALB/c control strains.
Conclusions: Our results demonstrate that NOD mice have a unique protein/peptide signature that are consistent with an activation of a local RAS prior to the onset of SjS-like hyposalivation which may contribute to the development of the disease.