The Proteomic Signature of Intestinal Acute Rejection in the Mouse
1
The Transplant Institute, Sahlgrenska University Hospital, 413 45 Gothenburg, Sweden
2
Laboratory for Transplantation and Regenerative Medicine, Institute of Clinical Sciences, Sahlgrenska Academy at the University of Gothenburg, Sahlgrenska Science Park Medicinaregatan 8, 413 90 Gothenburg, Sweden
3
First Surgical Clinic, Str. Clinicilor 3-5, 400006 Cluj-Napoca, Romania
4
Faculty of Medicine, University of Medicine and Pharmacy Cluj-Napoca, 400000 Cluj-Napoca, Romania
5
Proteomics Core Facility, Sahlgrenska Academy, University of Gothenburg, Medicinaregatan 5, 413 90 Gothenburg, Sweden
6
Wallenberg Laboratory, Department of Molecular and Clinical Medicine, Sahlgrenska Academy, University of Gothenburg, 413 45 Gothenburg, Sweden
7
Sahlgrenska Center for Cancer Research, Department of Laboratory Medicine, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, 405 30 Gothenburg, Sweden
8
Department of Surgery, Institute of Clinical Sciences, Sahlgrenska Academy, the University of Gothenburg, 413 45 Gothenburg, Sweden
9
Bioinformatics Core Facility, University of Gothenburg, Medicinaregatan 5, 413 90 Gothenburg, Sweden
*
Author to whom correspondence should be addressed.
Academic Editor: Amedeo Lonardo
Metabolites 2022, 12(1), 23; https://doi.org/10.3390/metabo12010023
Received: 30 October 2021
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Revised: 23 December 2021
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Accepted: 23 December 2021
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Published: 27 December 2021
(This article belongs to the Special Issue Hemorheology and Metabolism)
Intestinal acute rejection (AR) lacks a reliable non-invasive biomarker and AR surveillance is conducted through frequent endoscopic biopsies. Although citrulline and calprotectin have been suggested as AR biomarkers, these have limited clinical value. Using a mouse model of intestinal transplantation (ITx), we performed a proteome-wide analysis and investigated rejection-related proteome changes that may eventually be used as biomarkers. ITx was performed in allogenic (Balb/C to C57Bl) and syngeneic (C57Bl) combinations. Graft samples were obtained three and six days after transplantation (n = 4/time point) and quantitative proteomic analysis with iTRAQ-labeling and mass spectrometry of whole tissue homogenates was performed. Histology showed moderate AR in all allografts post-transplantation at day six. Nine hundred and thirty-eight proteins with at least three unique peptides were identified in the intestinal grafts. Eighty-six proteins varying by >20% between time points and/or groups had an alteration pattern unique to the rejecting allografts: thirty-seven proteins and enzymes (including S100-A8 and IDO-1) were significantly upregulated whereas forty-nine (among other chromogranin, ornithine aminotransferase, and arginase) were downregulated. Numerous proteins showed altered expression during intestinal AR, several of which were previously identified to be involved in acute rejection, although our results also identified previously unreported proteome changes. The metabolites and downstream metabolic pathways of some of these proteins and enzymes may become potential biomarkers for intestinal AR.
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Keywords:
intestinal transplantation; rejection; biomarkers; enzymes; chromogranin A
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MDPI and ACS Style
Oltean, M.; Bagge, J.; Dindelegan, G.; Kenny, D.; Molinaro, A.; Hellström, M.; Nilsson, O.; Sihlbom, C.; Casselbrant, A.; Davila, M.; Olausson, M. The Proteomic Signature of Intestinal Acute Rejection in the Mouse. Metabolites 2022, 12, 23. https://doi.org/10.3390/metabo12010023
AMA Style
Oltean M, Bagge J, Dindelegan G, Kenny D, Molinaro A, Hellström M, Nilsson O, Sihlbom C, Casselbrant A, Davila M, Olausson M. The Proteomic Signature of Intestinal Acute Rejection in the Mouse. Metabolites. 2022; 12(1):23. https://doi.org/10.3390/metabo12010023
Chicago/Turabian StyleOltean, Mihai, Jasmine Bagge, George Dindelegan, Diarmuid Kenny, Antonio Molinaro, Mats Hellström, Ola Nilsson, Carina Sihlbom, Anna Casselbrant, Marcela Davila, and Michael Olausson. 2022. "The Proteomic Signature of Intestinal Acute Rejection in the Mouse" Metabolites 12, no. 1: 23. https://doi.org/10.3390/metabo12010023
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