P038 Notch pathway in fibrosis: a new anti-fibrotic therapy in Crohn's disease?
نویسندگان
چکیده
Abstract Background Fibrosis represent the main complications related to Crohn's disease (CD). Notch signalling mediate fibrogenic process, including epithelial-mesenchymal transition (EMT) and fibroblast senescence but its role in CD fibrosis is currently unknown. Previous studies have shown a high expression of NOTCH4, NOTCH3, DLL3 DLL4 fibrotic tissue. mainly activates transcription factors involved EMT, macrophages could act as possible source (Edo, et al., 2022. JCC (i200)).The general aim present study determine potential pathway therapeutic target intestinal associated with CD. Specifically, we pretend: analyze localization NOTCH3/4 receptors tissue patients complicated; relevance EMT; fibroblast. Methods We analyzed samples from complicated lesions: by IH protein markers (BCL2 P53) WB. carry out vitro analyze: HES1 (effector pathway) EMT DLL4-HT29 treated cells transfected miNOTCH3 or miNOTCH4; proteins HSIF fibroblasts DLL3. Results NOTCH3 was located preferentially muscular areas -muscularis mucosa, endothelium muscularis externa- striking staining infiltrated mucosa unaffected area. NOTCH4 found more specifically crypts well lamina propria mucosa. The showed elevated levels BCL2 P53, compared same patient. increased HT29 cells, silencing significantly reverted these markers. produced no significant changes after treatment. DLL3, not DLL4, increase BCL2, vehicle (Figure). Conclusion NOTCH regulation key cellular functions processes essential for pathogenesis patients. DLL4-NOTCH4 interaction triggers mesenchymal epithelial colonic while seems relevant activation fibroblasts.
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ژورنال
عنوان ژورنال: Journal of Crohn's and Colitis
سال: 2023
ISSN: ['1876-4479', '1873-9946']
DOI: https://doi.org/10.1093/ecco-jcc/jjac190.0168