Salivary Proteome and Peptidome Profiling in Type 1 Diabetes Mellitus Using a Quantitative Approach

In
the present study, we applied iTRAQ-based quantitative approach to
explore the salivary proteome and peptidome profile in selected subjects
with type 1 diabetes, with and without microvascular complications,
aiming to identify disease-related markers. From a total of 434 distinct
proteins, bactericidal/permeability-increasing protein-like 1 and
pancreatic adenocarcinoma up-regulated factor were found in higher
levels in the saliva of all patients while increased content of other
proteins like alpha-2-macroglobulin, defensin alpha 3 neutrophil-specific,
leukocyte elastase inhibitor, matrix metalloproteinase-9, neutrophil
elastase, plastin-2, protein S100-A8 and protein S100-A9 were related
with microvascular complications as retinopathy and nephropathy. Protein–protein
interaction network analysis suggests the functional clusters defense,
inflammation and response to wounding as the most significantly associated
with type 1 diabetes pathogenesis. Peptidome data not only support
a diabetes-related higher susceptibility of salivary proteins to proteolysis
(mainly of aPRP, bPRP1 and bPRP2), but also evidenced an increased
content of some specific protein fragments known to be related with
bacterial attachment and the accumulation of phosphopeptides involved
in tooth protection. Overall, the salivary protein and peptide profile
highlights the importance of the innate immune system in the pathogenesis
of type 1 diabetes mellitus and related complications. This study
provides an integrated perspective of salivary proteome and peptidome
that should be further explored in future studies targeting specific
disease markers.