Proteomics and Imaging in Crohn’s Disease: TAILS of Unlikely Allies

Mainoli, Barbara; Hirota, Simon A.; Edgington-Mitchell, Laura E.; Lu, Catherine P.; Dufour, Antoine

doi:10.1016/j.tips.2019.11.008

Cited by 10 publications

(11 citation statements)

References 52 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Our current proteomic analysis has revealed enrichment of several newly associated but also previously reported proteases and protease inhibitors in SS. The activity of cysteine proteases (cathepsins) and serine proteases (neutrophil elastase, prostasin, proteinase-3/myeloblastin) could be further investigated using activity-based probes in SS ( Edgington-Mitchell et al, 2017 ; Anderson et al, 2019 , 2020 ; Mainoli et al, 2020 ; Mountford et al, 2020 ; Tu et al, 2021 ). The upregulation of cathepsin G in the saliva of patients with SS is likely associated with an increase in neutrophils and corresponds to an elevation in synovial fluid of RA patients ( Gao, 2018 ).…”

Section: Discussionmentioning

confidence: 99%

“…Interestingly, upregulation of several cysteine protease inhibitors in the saliva of healthy controls included cystatin-D, cystatin-S and cystatin-SN, indicating a possible regulation and inhibition of cathepsin activity ( Balbín et al, 1994 ). Further studies to characterize these proteases enriched in SS tears and saliva using N-terminomics could identify their potential substrates, which could help find new drug targets in SS ( Dufour, 2015 ; Mainoli et al, 2020 ; Longxiang Wang, Kimberly Main, Henry; Wang, Olivier Julien, 2021 ). Our data present new proteases, metabolic and cellular signaling pathways that are elevated in SS and could lead to unbiased investigations of new regulators of SS pathogenesis.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Proteomics Analysis of Tears and Saliva From Sjogren’s Syndrome Patients

et al. 2021

Self Cite

View full text Add to dashboard Cite

Sjogren’s syndrome (SS) is characterized by dysfunctional mucous membranes and dysregulated moisture-secreting glands resulting in various symptoms, including dry mouth and dry eyes. Here, we wanted to profile and compare the tear and saliva proteomes of SS patients to healthy controls. Tear and saliva samples were collected and subjected to an isotopic dimethylation labeling shotgun proteomics workflow to identify alterations in protein levels. In tear samples, we identified 83 upregulated and 112 downregulated proteins. Pathway enrichment analysis of the changing proteins by Metascape identified leukocyte transendothelial migration, neutrophil degranulation, and post-translation protein phosphorylation in tears of SS patients. In healthy controls’ tears, an enrichment for proteins related to glycolysis, amino acid metabolism and apoptotic signaling pathway were identified. In saliva, we identified 108 upregulated and 45 downregulated proteins. Altered pathways in SS patients’ saliva included cornification, sensory perception to taste and neutrophil degranulation. In healthy controls’ saliva, an enrichment for proteins related to JAK-STAT signaling after interleukin-12 stimulation, phagocytosis and glycolysis in senescence were identified. Dysregulated protease activity is implicated in the initiation of inflammation and immune cell recruitment in SS. We identified 20 proteases and protease inhibitors in tears and 18 in saliva which are differentially expressed between SS patients and healthy controls. Next, we quantified endogenous proteoglycan 4 (PRG4), a mucin-like glycoprotein, in tear wash and saliva samples via a bead-based immune assay. We identified decreased levels of PRG4 in SS patients’ tear wash compared to normal samples. Conversely, in saliva, we found elevated levels of PRG4 concentration and visualized PRG4 expression in human parotid gland via immunohistological staining. These findings will improve our mechanistic understanding of the disease and changes in SS patients’ protein expression will help identify new potential drug targets. PRG4 is among the promising targets, which we identified here, in saliva, for the first time.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Proteomics Analysis of Tears and Saliva From Sjogren’s Syndrome Patients

et al. 2021

Self Cite

View full text Add to dashboard Cite

show abstract

“…Proteases have vital and complex roles in the pathogenesis of inflammatory and autoimmune diseases, including Crohn’s disease. Cleaved or degraded proteins may cause activation, inactivation, altered receptor specificity, or other downstream effects . Further, proteolytic homeostasis is dysregulated under inflammatory or fibrotic conditions, which may affect concentrations of substrate proteins.…”

Section: Visualizing Protease Activity In Vitro In Vivo and Ex Vivomentioning

confidence: 99%

Biochemical Tools for Tracking Proteolysis

et al. 2021

Self Cite

View full text Add to dashboard Cite

All living organisms depend on tightly regulated cellular networks to control biological functions. Proteolysis is an important irreversible post-translational modification that regulates most, if not all, cellular processes. Proteases are a large family of enzymes that perform hydrolysis of protein substrates, leading to protein activation or degradation. The 473 known and 90 putative human proteases are divided into 5 main mechanistic groups: metalloproteases, serine proteases, cysteine proteases, threonine proteases, and aspartic acid proteases. Proteases are fundamental to all biological systems, and when dysregulated they profoundly influence disease progression. Inhibiting proteases has led to effective therapies for viral infections, cardiovascular disorders, and blood coagulation just to name a few. Between 5 and 10% of all pharmaceutical targets are proteases, despite limited knowledge about their biological roles. More than 50% of all human proteases have no known substrates. We present here a comprehensive list of all current known human proteases. We also present current and novel biochemical tools to characterize protease functions in vitro, in vivo, and ex vivo. These tools make it achievable to define both beneficial and detrimental activities of proteases in health and disease.

show abstract

“…The study identified lysine-acetylated sites on both host and microbial proteins that were differentially abundant in patients with Crohn's disease and healthy controls. Another form of PTMs is proteolytic processing of proteins by proteases, which act in concerted networks to amplify regulatory signals and are hypothesized to be molecular effectors involved in all aspects of biology, including microbiota homeostasis [93] Dysregulated proteolysis is often implicated in the initiation of inflammation but also persist in chronic inflammatory diseases [94] , [95] . Using an N-terminomics approach that enriches N-termini to determine protein cut by proteases, TAILS (terminal amine isotopic labelling of substrates) was used to profile human colonic mucosal biopsies where over 1642 human N-termini were identified [96] .…”

Section: Current Challenges Of Stool-based Metaproteomicsmentioning

confidence: 99%

Inferring early-life host and microbiome functions by mass spectrometry-based metaproteomics and metabolomics

Pettersen

Antunes

Dufour

et al. 2022

Computational and Structural Biotechnology Journal

Self Cite

View full text Add to dashboard Cite

Humans have a long-standing coexistence with microorganisms. In particular, the microbial community that populates the human gastrointestinal tract has emerged as a critical player in governing human health and disease. DNA and RNA sequencing techniques that map taxonomical composition and genomic potential of the gut community have become invaluable for microbiome research. However, deriving a biochemical understanding of how activities of the gut microbiome shape host development and physiology requires an expanded experimental design that goes beyond these approaches. In this review, we explore advances in high-throughput techniques based on liquid chromatography–mass spectrometry. These omics methods for the identification of proteins and metabolites have enabled direct characterisation of gut microbiome functions and the crosstalk with the host. We discuss current metaproteomics and metabolomics workflows for producing functional profiles, the existing methodological challenges and limitations, and recent studies utilising these techniques with a special focus on early life gut microbiome.

show abstract

Proteomics and Imaging in Crohn’s Disease: TAILS of Unlikely Allies

Cited by 10 publications

References 52 publications

Proteomics Analysis of Tears and Saliva From Sjogren’s Syndrome Patients

Proteomics Analysis of Tears and Saliva From Sjogren’s Syndrome Patients

Biochemical Tools for Tracking Proteolysis

Inferring early-life host and microbiome functions by mass spectrometry-based metaproteomics and metabolomics

Contact Info

Product

Resources

About