Intestinal proteomic analysis of a novel non-human primate model of experimental colitis reveals signatures of mitochondrial and metabolic dysfunction.
Journal
Mucosal immunology
ISSN: 1935-3456
Titre abrégé: Mucosal Immunol
Pays: United States
ID NLM: 101299742
Informations de publication
Date de publication:
11 2019
11 2019
Historique:
received:
24
04
2019
accepted:
21
08
2019
revised:
15
08
2019
pubmed:
5
9
2019
medline:
28
4
2020
entrez:
5
9
2019
Statut:
ppublish
Résumé
Animal models recapitulating features of chronic colitis, such as ulcerative colitis, Crohn's disease, or HIV infection, are critical to study disease pathogenesis and test novel therapeutics. In this study, we used a proteomics approach to explore the molecular intestinal response in two rhesus macaque (RM) animal models of experimentally induced colitis using dextran sulfate sodium (DSS) and simian immunodeficiency virus (SIV) infection. Proteomic analysis detected more than 2500 proteins in colonic tissue collected from 30 RMs. Differential protein expression analysis revealed a protein expression pattern in DSS-treated RMs resembling the proteome of human ulcerative colitis. In a group of 12 DSS-treated RMs compared to 6 with no treatment, decrease in expression of proteins related to mitochondrial energy metabolism, including fatty acid metabolism was noted, while innate immune activation pathways, including complement and coagulation proteins were upregulated. SIV infection of RMs resulted in increased innate immune responses related to viral defense. Proteomic signatures of barrier damage were apparent in both DSS treatment or SIV infection. These results demonstrate that DSS treatment in a non-human primate model resembles features of human ulcerative colitis, making this a promising tool to study important immunological mechanisms in inflammatory bowel disease.
Identifiants
pubmed: 31481749
doi: 10.1038/s41385-019-0200-2
pii: S1933-0219(22)00453-6
pmc: PMC7673647
mid: NIHMS1637079
doi:
Substances chimiques
Dextran Sulfate
9042-14-2
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
1327-1335Subventions
Organisme : NIH HHS
ID : P51 OD011092
Pays : United States
Organisme : NIDDK NIH HHS
ID : K08 DK110415
Pays : United States
Organisme : NCI NIH HHS
ID : HHSN261200800001E
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK112254
Pays : United States
Organisme : CCR NIH HHS
ID : HHSN261200800001C
Pays : United States
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