Biology subjects

Edman, M. C.

Publications and source records attributed to Edman, M. C..

2 recordsLinked to original sources

bioRxiv2026

Tear Proteomics Reveals RAGE and NLRP3 Inflammasome Pathway Activation in Lacrimal Glands of a Sjögren's Disease Mouse Model

PurposeTo characterize tear proteome changes in male non-obese diabetic (NOD) mice with Sjogrens disease (SjD)-like autoimmune dacryoadenitis and determine whether identified tear proteins are associated with lacrimal gland (LG) pathogenesis. MethodsTears were collected from 14-week-old male NOD mice and age-matched male BALB/c controls and analyzed by tandem mass tag (TMT)-based liquid chromatography tandem mass spectrometry (LC-MS/MS). Differentially expressed proteins (DEPs) were defined using adjusted P < 0.05 and absolute fold change > 1.5. Functional enrichment analysis was performed using Enrichr. Selected upregulated DEPs were further examined in tear and LG samples from independent mouse cohorts using Western blotting, immunofluorescence, and RT-qPCR. ResultsA total of 142 proteins were quantified across all tear samples. Hierarchical clustering and principal component analysis (PCA) separated NOD from BALB/c tear proteomes. A total of 41 proteins were differentially expressed in NOD mouse tears (33 increased, 8 decreased). Increased tear proteins were enriched in immune and inflammatory responses, secretory compartments, RAGE receptor binding, glutathione metabolism, oxidative stress, and redox regulation. S100A8/A9, GSTO1-1, Gal-3, and pIgR/secretory component (SC) were increased in both NOD mouse tears and LG. In NOD LG, increased S100A8/A9 was accompanied by elevated RAGE, whereas increased GSTO1-1 was associated with increased NLRP3, cleaved caspase-1, cleaved gasdermin, cleaved IL-1{beta}, and increased Il1b, Il18, and Il18r gene expression. ConclusionsMale NOD mouse tears contain disease-related proteins reflecting pathological inflammatory and epithelial changes in the LG including increased RAGE signaling, NLRP3 inflammasome activation, and altered epithelial transcytosis.

immunology↗

bioRxiv2021

Tear miRNAs identified in a murine model of Sjögren's Syndrome as potential diagnostic biomarkers and indicators of disease mechanism

ObjectiveThe tear miRNAome of the male NOD mouse, a model of ocular symptoms of Sjogrens syndrome (SS), was analyzed to identify possible tear biomarkers of the disease. MethodsMale NOD mice, aged 12-14 weeks, were used to identify tear miRNAs associated with development of autoimmune dacryoadenitis. Age-matched female NOD mice that do not develop the autoimmune dacryoadenitis characteristic of SS were used as negative controls while age- and sex-matched male BALB/c mice served as healthy controls. Total RNA was isolated from stimulated tears pooled from 5 mice per sample and tear miRNAs were sequenced and analyzed. Putative miRNA hits were validated using RT-qPCR in a separate mouse cohort, and the pathways influenced by the validated hits were identified using Ingenuity Pathway Analysis. ResultsIn comparison to tears from both healthy (male BALB/c) and negative control (female NOD) mice, initial analysis identified 7 upregulated and 7 downregulated miRNAs in male NOD mouse tears. Of these, 8 were subsequently validated by RT-qPCR in tears from additional mouse cohorts. miRNAs previously implicated in SS pathology included mmu-miR-146a/b-5p, which were significantly downregulated in the male NOD mouse tears, as well as mmu-miR-150-5p and mmu-miR-181a-5p, which were upregulated in the male NOD mouse tears. All other validated hits including the upregulated miR-181b-5p and mmu-miR-203-3p, as well as the downregulated mmu-miR-322-5p and mmu-miR-503-5p, represent novel putative indicators of autoimmune dacryoadenitis in SS. ConclusionsA panel of differentially expressed miRNAs were identified in tears of SS model male NOD mice, including some never previously linked to SS. These may have potential utility as diagnostic biomarkers for ocular symptoms of SS; evaluation of the pathways influenced by these dysregulated miRNAs may also provide further insights into SS pathogenesis.

immunology↗