Degradation of the extracellular matrix is part of the pathology of ulcerative colitis

Stefan Kirov*, Ariella Sasson, Clarence Zhang, Scott Chasalow, Ashok Dongre, Hanno Steen, Allan Stensballe, Vibeke Andersen, Svend Birkelund, Tue Bjerg Bennike

*Kontaktforfatter for dette arbejde

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Resumé

The scientific value of re-analyzing existing datasets is often proportional to the complexity of the data. Proteomics data are inherently complex and can be analyzed at many levels, including proteins, peptides, and post-translational modifications to verify and/or develop new hypotheses. In this paper, we present our re-analysis of a previously published study comparing colon biopsy samples from ulcerative colitis (UC) patients to non-affected controls. We used a different statistical approach, employing a linear mixed-effects regression model and analyzed the data both on the protein and peptide level. In addition to confirming and reinforcing the original finding of upregulation of neutrophil extracellular traps (NETs), we report novel findings, including that Extracellular Matrix (ECM) degradation and neutrophil maturation are involved in the pathology of UC. The pharmaceutically most relevant differential protein expressions were confirmed using immunohistochemistry as an orthogonal method. As part of this study, we also compared proteomics data to previously published mRNA expression data. These comparisons indicated compensatory regulation at transcription levels of the ECM proteins we identified and open possible new avenues for drug discovery.

OriginalsprogEngelsk
TidsskriftMolecular Omics
Vol/bind15
Udgave nummer1
Sider (fra-til)67-76
ISSN2515-4184
DOI
StatusUdgivet - jan. 2019

Fingeraftryk

Ulcerative Colitis
Pathology
Peptides
Extracellular Matrix Proteins
Colon
Proteins
Neutrophils
Up-Regulation
Messenger RNA
Datasets
Extracellular Traps

Citer dette

Kirov, S., Sasson, A., Zhang, C., Chasalow, S., Dongre, A., Steen, H., ... Bennike, T. B. (2019). Degradation of the extracellular matrix is part of the pathology of ulcerative colitis. Molecular Omics, 15(1), 67-76. https://doi.org/10.1039/c8mo00239h
Kirov, Stefan ; Sasson, Ariella ; Zhang, Clarence ; Chasalow, Scott ; Dongre, Ashok ; Steen, Hanno ; Stensballe, Allan ; Andersen, Vibeke ; Birkelund, Svend ; Bennike, Tue Bjerg. / Degradation of the extracellular matrix is part of the pathology of ulcerative colitis. I: Molecular Omics. 2019 ; Bind 15, Nr. 1. s. 67-76.
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abstract = "The scientific value of re-analyzing existing datasets is often proportional to the complexity of the data. Proteomics data are inherently complex and can be analyzed at many levels, including proteins, peptides, and post-translational modifications to verify and/or develop new hypotheses. In this paper, we present our re-analysis of a previously published study comparing colon biopsy samples from ulcerative colitis (UC) patients to non-affected controls. We used a different statistical approach, employing a linear mixed-effects regression model and analyzed the data both on the protein and peptide level. In addition to confirming and reinforcing the original finding of upregulation of neutrophil extracellular traps (NETs), we report novel findings, including that Extracellular Matrix (ECM) degradation and neutrophil maturation are involved in the pathology of UC. The pharmaceutically most relevant differential protein expressions were confirmed using immunohistochemistry as an orthogonal method. As part of this study, we also compared proteomics data to previously published mRNA expression data. These comparisons indicated compensatory regulation at transcription levels of the ECM proteins we identified and open possible new avenues for drug discovery.",
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author = "Stefan Kirov and Ariella Sasson and Clarence Zhang and Scott Chasalow and Ashok Dongre and Hanno Steen and Allan Stensballe and Vibeke Andersen and Svend Birkelund and Bennike, {Tue Bjerg}",
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Kirov, S, Sasson, A, Zhang, C, Chasalow, S, Dongre, A, Steen, H, Stensballe, A, Andersen, V, Birkelund, S & Bennike, TB 2019, 'Degradation of the extracellular matrix is part of the pathology of ulcerative colitis', Molecular Omics, bind 15, nr. 1, s. 67-76. https://doi.org/10.1039/c8mo00239h

Degradation of the extracellular matrix is part of the pathology of ulcerative colitis. / Kirov, Stefan; Sasson, Ariella; Zhang, Clarence; Chasalow, Scott; Dongre, Ashok; Steen, Hanno; Stensballe, Allan; Andersen, Vibeke; Birkelund, Svend; Bennike, Tue Bjerg.

I: Molecular Omics, Bind 15, Nr. 1, 01.2019, s. 67-76.

Publikation: Bidrag til tidsskriftReviewForskningpeer review

TY - JOUR

T1 - Degradation of the extracellular matrix is part of the pathology of ulcerative colitis

AU - Kirov, Stefan

AU - Sasson, Ariella

AU - Zhang, Clarence

AU - Chasalow, Scott

AU - Dongre, Ashok

AU - Steen, Hanno

AU - Stensballe, Allan

AU - Andersen, Vibeke

AU - Birkelund, Svend

AU - Bennike, Tue Bjerg

PY - 2019/1

Y1 - 2019/1

N2 - The scientific value of re-analyzing existing datasets is often proportional to the complexity of the data. Proteomics data are inherently complex and can be analyzed at many levels, including proteins, peptides, and post-translational modifications to verify and/or develop new hypotheses. In this paper, we present our re-analysis of a previously published study comparing colon biopsy samples from ulcerative colitis (UC) patients to non-affected controls. We used a different statistical approach, employing a linear mixed-effects regression model and analyzed the data both on the protein and peptide level. In addition to confirming and reinforcing the original finding of upregulation of neutrophil extracellular traps (NETs), we report novel findings, including that Extracellular Matrix (ECM) degradation and neutrophil maturation are involved in the pathology of UC. The pharmaceutically most relevant differential protein expressions were confirmed using immunohistochemistry as an orthogonal method. As part of this study, we also compared proteomics data to previously published mRNA expression data. These comparisons indicated compensatory regulation at transcription levels of the ECM proteins we identified and open possible new avenues for drug discovery.

AB - The scientific value of re-analyzing existing datasets is often proportional to the complexity of the data. Proteomics data are inherently complex and can be analyzed at many levels, including proteins, peptides, and post-translational modifications to verify and/or develop new hypotheses. In this paper, we present our re-analysis of a previously published study comparing colon biopsy samples from ulcerative colitis (UC) patients to non-affected controls. We used a different statistical approach, employing a linear mixed-effects regression model and analyzed the data both on the protein and peptide level. In addition to confirming and reinforcing the original finding of upregulation of neutrophil extracellular traps (NETs), we report novel findings, including that Extracellular Matrix (ECM) degradation and neutrophil maturation are involved in the pathology of UC. The pharmaceutically most relevant differential protein expressions were confirmed using immunohistochemistry as an orthogonal method. As part of this study, we also compared proteomics data to previously published mRNA expression data. These comparisons indicated compensatory regulation at transcription levels of the ECM proteins we identified and open possible new avenues for drug discovery.

KW - Biopsy

KW - Case-Control Studies

KW - Colitis, Ulcerative/metabolism

KW - Colon/metabolism

KW - Extracellular Matrix/metabolism

KW - Humans

KW - Hydroxyproline/metabolism

KW - Proteins/genetics

KW - Quality Control

U2 - 10.1039/c8mo00239h

DO - 10.1039/c8mo00239h

M3 - Review

C2 - 30702115

AN - SCOPUS:85061230866

VL - 15

SP - 67

EP - 76

JO - Molecular Omics

JF - Molecular Omics

SN - 2515-4184

IS - 1

ER -

Kirov S, Sasson A, Zhang C, Chasalow S, Dongre A, Steen H et al. Degradation of the extracellular matrix is part of the pathology of ulcerative colitis. Molecular Omics. 2019 jan;15(1):67-76. https://doi.org/10.1039/c8mo00239h