Janker, Lukas and Schuster, Dina and Bortel, Patricia and Hagn, Gerhard and Meier-Menches, Samuel M. and Mohr, Thomas and Mader, Johanna C. and Slany, Astrid and Bileck, Andrea and Brunmair, Julia and Madl, Christian and Unger, Lukas and Hennlich, Barbara and Weitmayr, Barbara and Del Favero, Giorgia and Pils, Dietmar and Pukrop, Tobias and Pfisterer, Nikolaus and Feichtenschlager, Thomas and Gerner, Christopher (2023) Multiomics-empowered Deep Phenotyping of Ulcerative Colitis Identifies Biomarker Signatures Reporting Functional Remission States. JOURNAL OF CROHNS & COLITIS, 17 (9). pp. 1514-1527. ISSN 1873-9946, 1876-4479
Full text not available from this repository. (Request a copy)Abstract
Introduction Ulcerative colitis [UC] is a chronic disease with rising incidence and unclear aetiology. Deep molecular phenotyping by multiomics analyses may provide novel insights into disease processes and characteristic features of remission states. Methods UC pathomechanisms were assessed by proteome profiling of human tissue specimens, obtained from five distinct colon locations for each of the 12 patients included in the study. Systemic disease-associated alterations were evaluated thanks to a cross-sectional setting of mass spectrometry-based multiomics analyses comprising proteins, metabolites, and eicosanoids of plasma obtained from UC patients during acute episodes and upon remission, in comparison with healthy controls. Results Tissue proteome profiling indicated colitis-associated activation of neutrophils, macrophages, B and T cells, fibroblasts, endothelial cells and platelets, and hypoxic stress, and suggested a general downregulation of mitochondrial proteins accompanying the establishment of apparent wound healing-promoting activities including scar formation. Whereas pro-inflammatory proteins were apparently upregulated by immune cells, the colitis-associated epithelial cells, fibroblasts, endothelial cells, and platelets seemed to predominantly contribute anti-inflammatory and wound healing-promoting proteins. Blood plasma proteomics indicated chronic inflammation and platelet activation, whereas plasma metabolomics identified disease-associated deregulations of gut and gut microbiome-derived metabolites. Upon remission several, but not all, molecular candidate biomarker levels recovered back to normal. Conclusion The findings may indicate that microvascular damage and platelet deregulation hardly resolve upon remission, but apparently persist as disease-associated molecular signatures. This study presents local and systemic molecular alterations integrated in a model for UC pathomechanisms, potentially supporting the assessment of disease and remission states in UC patients.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | INFLAMMATORY-BOWEL-DISEASE; ENDOTHELIAL-CELLS; HUMAN FIBROBLASTS; NATURAL-HISTORY; OMICS ANALYSIS; PROTEOME; THERAPY; CANCER; SUSCEPTIBILITY; HEPATOCYTES; Multi-omics; tissue proteomics; oxylipins; metabolomics; blood plasma |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Innere Medizin III (Hämatologie und Internistische Onkologie) |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 23 Mar 2024 09:27 |
| Last Modified: | 23 Mar 2024 09:27 |
| URI: | https://pred.uni-regensburg.de/id/eprint/60398 |
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