Gelsolin as a Potential Biomarker for Endoscopic Activity and Mucosal Healing in Ulcerative Colitis

Maeda, Keiko; Nakamura, Masanao; Yamamura, Takeshi; Sawada, Tsunaki; Ishikawa, Eri; Oishi, Akina; Ikegami, Shuji; Kakushima, Naomi; Iida, Tadashi; Mizutani, Yasuyuki; Ishikawa, Takuya; Ohno, Eizaburo; Honda, Takashi; Ishigami, Masatoshi

doi:10.3390/biomedicines10040872

Cited by 5 publications

(7 citation statements)

References 35 publications

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“…Among the 90 unique MOA proteins of pathogens’ association with IBD (see Table S1.3 , union of all MOA proteins), ITGB1 and GSN have the largest numbers (6 and 5 of 13) of interacting pathogens. ITGB1 plays an important role in the pathogenesis of IBD 45 ; GSN is a potential biomarker for ulcerative colitis 46 .…”

Section: Resultsmentioning

confidence: 99%

PHEVIR: an artificial intelligence algorithm that predicts the molecular role of pathogens in complex human diseases

Zhou

Astore

Skolnick

2022

Sci Rep

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Infectious diseases are known to cause a wide variety of post-infection complications. However, it’s been challenging to identify which diseases are most associated with a given pathogen infection. Using the recently developed LeMeDISCO approach that predicts comorbid diseases associated with a given set of putative mode of action (MOA) proteins and pathogen-human protein interactomes, we developed PHEVIR, an algorithm which predicts the corresponding human disease comorbidities of 312 viruses and 57 bacteria. These predictions provide an understanding of the molecular bases of complications and means of identifying appropriate drug targets to treat them. As an illustration of its power, PHEVIR is applied to identify putative driver pathogens and corresponding human MOA proteins for Type 2 diabetes, atherosclerosis, Alzheimer’s disease, and inflammatory bowel disease. Additionally, we explore the origins of the oncogenicity/oncolyticity of certain pathogens and the relationship between heart disease and influenza. The full PHEVIR database is available at https://sites.gatech.edu/cssb/phevir/.

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Section: Resultsmentioning

confidence: 99%

PHEVIR: an artificial intelligence algorithm that predicts the molecular role of pathogens in complex human diseases

Zhou

Astore

Skolnick

2022

Sci Rep

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“…Gelsolin is the second most significant differentiating protein between dogs with CE and controls in our study with fold change 14.8 ( P < .001). This protein is proposed to be a potential biomarker for ulcerative colitis and inflammation in people to predict disease severity, treatment efficacy, and clinical outcomes 52‐54 . Gelsolin is a multifunctional protein and has an important role in cytoskeletal remodeling including actin filament severing, capping and nucleating activity 52‐54 .…”

Section: Discussionmentioning

confidence: 99%

“…This protein is proposed to be a potential biomarker for ulcerative colitis and inflammation in people to predict disease severity, treatment efficacy, and clinical outcomes. 52 , 53 , 54 Gelsolin is a multifunctional protein and has an important role in cytoskeletal remodeling including actin filament severing, capping and nucleating activity. 52 , 53 , 54 It correlates with clinical and endoscopic activities and has a higher sensitivity and specificity than C‐reactive protein for diagnosing ulcerative colitis in humans.…”

Section: Discussionmentioning

confidence: 99%

“… 52 , 53 , 54 Gelsolin is a multifunctional protein and has an important role in cytoskeletal remodeling including actin filament severing, capping and nucleating activity. 52 , 53 , 54 It correlates with clinical and endoscopic activities and has a higher sensitivity and specificity than C‐reactive protein for diagnosing ulcerative colitis in humans. 52 In contrast to our finding where gelsolin was higher in diseased dogs, gelsolin has an inverse relationship with clinical and endoscopic activity in patients with ulcerative colitis, its level was significantly lower in ulcerative colitis patients compared to healthy controls.…”

Section: Discussionmentioning

confidence: 99%

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Serum proteome of dogs with chronic enteropathy

Ruaux

Griebsch

et al. 2023

Veterinary Internal Medicne

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Background: Chronic enteropathy (CE) is common in dogs and can occur with multiple etiologies including food-responsive enteropathy (FRE) and idiopathic inflammatory bowel disease (IBD).Hypothesis/Objective: To study the protein profile and pathway differences among dogs with FRE, IBD, and healthy controls using serum proteome analysis.Animals: Nine CE dogs with signs of gastrointestinal disease and histologically confirmed chronic inflammatory enteropathy and 16 healthy controls. Methods:A cross-sectional study with cases recruited from 2 veterinary hospitals between May 2019 and November 2020 was performed. Serum samples were analyzed using mass spectrometry-based proteomic techniques.Results: Proteomic profiles showed marked variation in relative protein abundances.Forty-five proteins were significantly (P ≤ .01) differentially expressed among the dogs with CE and controls with ≥2-fold change in abundance. The fold change of dogs with IBD normalized to controls was more pronounced for the majority of proteins than that seen in the dogs with FRE normalized to control dogs. Proteins involving reactive oxygen species, cytokine activation, acute phase response signaling, and lipid metabolism were altered in dogs with CE.Conclusions and Clinical Importance: Cytokine alterations, acute phase response signaling, and lipid metabolism are likely involved in pathogenesis of CE. Although there are insufficient current data to justify the use of proteomic biomarkers for assessment of CE in dogs, our study identifies potential candidates.

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“…Recent studies have pointed to a significant degree of concordance (between peripheral whole blood and colonic tissue in paediatric patients with IBD 9. In addition, blood-based biomarkers have been identified and suggested as surrogate markers of mucosal healing and endoscopic response in Ulcerative colitis10 11 as well as predictors of anti-TNFα non-response in IBD 12. CD4 T-cells and monocyte-derived macrophages not only play a critical role in mediating disease pathogenesis at the primary disease site(s), but also are known to be altered with respect to their activity in the blood circulatory system 13–15.…”

Section: Introductionmentioning

confidence: 99%

Distinct transcriptional signatures in purified circulating immune cells drive heterogeneity in disease location in IBD

Verstockt

Cremer

et al. 2023

BMJ Open Gastroenterol

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ObjectiveTo infer potential mechanisms driving disease subtypes among patients with inflammatory bowel disease (IBD), we profiled the transcriptome of purified circulating monocytes and CD4 T-cells.DesignRNA extracted from purified monocytes and CD4 T-cells derived from the peripheral blood of 125 endoscopically active patients with IBD was sequenced using Illumina HiSeq 4000NGS. We used complementary supervised and unsupervised analytical methods to infer gene expression signatures associated with demographic/clinical features. Expression differences and specificity were validated by comparison with publicly available single cell datasets, tissue-specific expression and meta-analyses. Drug target information, druggability and adverse reaction records were used to prioritise disease subtype-specific therapeutic targets.ResultsUnsupervised/supervised methods identified significant differences in the expression profiles of CD4 T-cells between patients with ileal Crohn’s disease (CD) and ulcerative colitis (UC). Following a pathway-based classification (Area Under Receiver Operating Characteristic - AUROC=86%) between ileal-CD and UC patients, we identified MAPK and FOXO pathways to be downregulated in UC. Coexpression module/regulatory network analysis using systems-biology approaches revealed mediatory core transcription factors. We independently confirmed that a subset of the disease location-associated signature is characterised by T-cell-specific and location-specific expression. Integration of drug-target information resulted in the discovery of several new (BCL6,GPR183,TNFAIP3) and repurposable drug targets (TUBB2A,PRKCQ) for ileal CD as well as novel targets (NAPEPLD,SLC35A1) for UC.ConclusionsTranscriptomic profiling of circulating CD4 T-cells in patients with IBD demonstrated marked molecular differences between the IBD-spectrum extremities (UC and predominantly ileal CD, sandwiching colonic CD), which could help in prioritising particular drug targets for IBD subtypes.

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Gelsolin as a Potential Biomarker for Endoscopic Activity and Mucosal Healing in Ulcerative Colitis

Cited by 5 publications

References 35 publications

PHEVIR: an artificial intelligence algorithm that predicts the molecular role of pathogens in complex human diseases

PHEVIR: an artificial intelligence algorithm that predicts the molecular role of pathogens in complex human diseases

Serum proteome of dogs with chronic enteropathy

Distinct transcriptional signatures in purified circulating immune cells drive heterogeneity in disease location in IBD

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