Autor: |
Weß, Veronika, Schuster-Winkelmann, Paula, Karatekin, Yasemin Hazal, Malik, Simge, Beigel, Florian, Kühn, Florian, Gropp, Roswitha |
Předmět: |
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Zdroj: |
International Journal of Molecular Sciences; Aug2023, Vol. 24 Issue 15, p12348, 19p |
Abstrakt: |
The development of animal models reflecting the pathologies of ulcerative colitis (UC) and Crohn's disease (CD) remains a major challenge. The NOD/SCID/IL2rγnull (NSG) mouse strain, which is immune-compromised, tolerates the engraftment of human peripheral blood mononuclear cells (PBMC) derived from patients with UC (NSG-UC) or CD (NSG-CD). This offers the opportunity to examine the impact of individual immunological background on the development of pathophysiological manifestations. When challenged with ethanol, NSG-UC mice exhibited a strong pro-inflammatory response, including the development of edemas, influx of human T cells, B cells and monocytes into the mucosa and submucosa, and elevated expression of the inflammatory markers CRP and CCL-7. Fibrotic alterations were characterized by an influx of fibroblasts and a thickening of the muscularis mucosae. In contrast, the development of pathological manifestations in NSG-CD mice developed without challenge and was signified by extensive collagen deposition between the muscularis propria and muscularis mucosae, as observed in the areas of strictures in CD patients. Vimentin-expressing fibroblasts supplanting colonic crypts and elevated expression of HGF and TGFß corroborated the remodeling phenotype. In summary, the NSG-UC and NSG-CD models partially reflect these human diseases and are powerful tools to examine the mechanism underlying the inflammatory processes in UC and CD. [ABSTRACT FROM AUTHOR] |
Databáze: |
Complementary Index |
Externí odkaz: |
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