P118 Induction of ETS1 and senescence associated secretory phenotype in human intestinal fibroblasts
نویسندگان
چکیده
Abstract Background Fibrosis is a complication commonly present in Crohn’s disease (CD) patients with structuring (B2) or penetrating (B3) behaviour, no available treatment. This process characterized by an excessive extracellular matrix deposition, mainly associated dysregulated function of myofibroblasts. We analyse here, the expression markers senescence human intestinal fibroblasts. Methods Human small fibroblasts (HSIF; P10760, Innoprot, Spain) were treated during 48h 2µg/mL DLL4, 20ng/ml TNFα, 2ng/ml IL-1β, 5ng/ml TGFβ1, and 100ng/ml of. In some cases, 20nM siRNA to ETS1 gene (siETS21) negative control (NC). Gene profiles analysed RT-qPCR. Results Treatment IL-1β significantly increased mRNA a) different senescence-associated secretory phenotype (SASP) factors (IL-1α, IL-8, Serpine1); b) metalloprotease ADAM12 chitinase CHI3L1 c) transcription factor related ETS proto-oncogene 1 (ETS1), all compared vehicle PDGF ADAM12, ETS1, PTEN factor, E2F5, while it induced non-significant increase such as P16, P21, P53 MCL1. TGFβ1 did not alter reported above only IGFBP3 gene, another SASP factor. Both DLL4 TNFα failed modify any markers. Finally, cellular model depletion showed that siETS1 basal conditions exhibited decreased levels IL-8 BCL2. Conclusion primary fibroblasts, treatment IL1b involved cell cycle arrest. The induction both treatments involvement this regulating conditions, suggest relevant role for activation
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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/jjac190.0248