Intest Res > Volume 21(3); 2023 > Article |
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Funding Source
Koh SJ was supported by a National Research Foundation of Korea grant funded by the Korea government (MSIT; No. 2019 R1C1C1002243) and the Basic Science Research Program through the National Research Foundation of Korea funded by the Ministry of Education (NRF-2016R1D1A1B03931961 and NRF-2020R1A1F10666419, NFR-2020R1F1A1066491).
Conflict of Interest
Radi ZA and Habtezion A are employees of Pfizer Inc. No potential conflict of interest relevant to this article was reported.
Author Contribution
Conceptualization: Koh SJ. Data curation: Lee CH. Investigation: Lee CH. Resources: Lee CH, Koh SJ. Supervision: Radi ZA, Habtezion A. Visualization: Lee CH. Writing - original draft: Lee CH, Koh SJ. Writing - review & editing: Lee CH, Koh SJ, Radi ZA, Habtezion A. Approval of final manuscript: all authors.
Model | Colitis | Fibrosis | Colitic cancer | Reference |
---|---|---|---|---|
DSS induced | • Most convenient and reproducible model of colitis | • Fibrosis could be driven by gut wound healing responses after epithelial injury in several murine strains | • DSS with azoxymethane is most widely used model inducing colitic cancer due to its rapidity and high penetrance | [15-18, 20-23] |
• Acute and chronic colitis could be induced by adjusting dosage and cycles of administration | ||||
Acetic acid induced | • Primarily acute colitis is induced by chemical injury and chronic colitis could be generated in dose and duration dependendent manner | • Despite very low incidence rate, fibrosis has been reported | • There is no definite study revealing acetic acid as appropriate model for inducing colitic cancer | [24-26] |
• Mimicking some features of UC with involvement of distal colon | ||||
Carrageenan | • Acute and chronic colitis could be induced resembling UC histopathologically | • Weak evidence of causing intestinal fibrosis | • Several studies demonstrate the association of colitic cancer | [27-30] |
• Applying to colitic cancer model is difficult due to its length of time | ||||
Peroxynitrite | • Intestinal transmural inflammation is accompanied by increment of nitric oxide and myeloperoxidase production | • Luminal narrowing and intestinal stenosis were detected in one study but further experiments are required to support this model for intestinal fibrosis | • There is no definite report suggesting peroxynitrite as appropriate model for developing colitic cancer | [12, 31] |
TNBS induced | • Colitis can be induced by haptenization in forms of acute and chronic inflammation resembling human CD | • One of the most commonly used animal model for studying intestinal fibrosis | • Several reports support that regular maintenance of TNBS could induce intestinal adenocarcinoma in mice | [32-35] |
• The susceptibility against TNBS induced colitis depends on types of transgenic mice | ||||
Oxazolone induced | • Intrarectal administration cause severe colitis in distal half of the colon which mimics human UC | • Weak evidence of causing intestinal fibrosis | • Oxazolone-induced colitis model has a limitation for investigating tumorigenesis due to its acute form of inflammation | [13, 36, 37] |
• Colitic cancer was developed using oxazolone-induced chronic model with azoxymethane in BALB/c mice |
Ahr, aryl hydrocarbon receptor; AGR2, anterior gradient protein 2 homolog; AP1B, adaptor protein 1B; ATF4, activating transcription factor; Bach2, broad complex-tramtrack-bric a brac and Cap’n’collar homology 2; Blimp, B-lymphocyte-induced maturation protein; Bach2, BTB domain and CNC homolog 2; C1galt1, core 1 synthase, glycoprotein-N-acetylgalactosamine 3-beta-galactosyltransferase 1; Casp8, caspase 8; CD4, CD4 positive T cells; Cbl-b, Casitas B cell lymphoma b; CRF, corticotropin-releasing factor; CX3CR1, CX3C motif chemokine receptor 1; DC, dendritic cells; epi, epithelial cells; GATA3, GATA binding protein 3; GARP, glycoprotein-A repetitions predominant protein; GPX1/2, glutathione peroxidases 1 and 2; IEC, intraepithelial lymphocytes; IKK, I kappa B kinase; iKO, inducible knockout; IL, Interleukin; IRE, inositol-requiring enzyme; Itch, itchy E3 ubiquitin protein ligase; KO, knockout; Lcn2, lipocalin-2; Mφ, macrophages; Mdr1α, multidrug resistance protein 1α; MHC, major histocompatibility complex; Muc2, mucin 2; NEMO, NF-kappa-B essential modulator; Nr2f6, nuclear receptor subfamily 2; group F, member 6; PDK1, 3-phosphoinositide-dependent protein kinase-1; Pggt1b, protein geranylgeranyl transferase type 1 subunit beta; PTPN11, tyrosine-protein phosphatase non-receptor type 11; Rhbdf2, rhomboid 5 homolog 2; ROR, RAR-related orphan receptor; SHIP, SH-2 containing inositol 5’ polyphosphatase; STAT, signal transducer and activator of transcription; TAK1, transforming growth factor-beta-activated kinase 1; TCR, T cell receptor; TGFβ, transforming growth factor beta; TLR, Toll-like receptor; Treg, regulatory T cell; TSC1, tuberous sclerosis complex 1; Uhrf1, ubiquitin-like, containing PHD and RING finger domains, 1; WASP, Wiskott-Aldrich syndrome protein.