FOSL1 knockdown ameliorates DSS‑induced inflammation and barrier damage in ulcerative colitis via MMP13 downregulation

Ma,Lizhuan; Zhang,Xiujing; Zhang,Chao; Hou,Bingxu; Zhao,Hongtao

doi:10.3892/etm.2022.11488

FOSL1 knockdown ameliorates DSS‑induced inflammation and barrier damage in ulcerative colitis via MMP13 downregulation

Authors:
- Lizhuan Ma
- Xiujing Zhang
- Chao Zhang
- Bingxu Hou
- Hongtao Zhao
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Affiliations: Department of Gastroenterology, North China University of Science and Technology Affiliated Hospital, Tangshan, Hebei 063000, P.R. China
Published online on: July 1, 2022 https://doi.org/10.3892/etm.2022.11488
Article Number: 551
Copyright: © Ma et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Ulcerative colitis (UC) is a chronic inflammatory disease of the colon. Fos‑related antigen 1 is highly expressed in mild UC and affects the maintenance and delayed recurrence of inflammatory bowel disease. Therefore the present study aimed to investigate the role of Fos‑like antigen‑1 (FOSL1) in UC. Use of the JASPAR database predicted the possible interaction of FOSL1 and the MMP13 promoter. FOSL1 and MMP13 mRNA and protein expression levels in dextran sodium sulfate (DSS)‑induced HT29 cells and colon tissues of a UC mice model were determined using reverse transcription‑quantitative PCR and western blotting, respectively. MMP13 promoter activity was determined using the dual‑luciferase reporter assay, the relationship between FOSL1 and MMP13 promoter was determined using chromatin immunoprecipitation, inflammatory factor levels were quantified using ELISA, cell monolayer permeability analysis was performed using transepithelial electrical resistance measurements and tight junction protein expression levels were determined by western blotting. After constructing a UC mice model, mice colonic injury was determined with the quantification of colon length, H&E staining and disease activity index. The results demonstrated that FOSL1 and MMP13 were upregulated in DSS‑induced HT29 cells and tissues. FOSL1 was also determined to be bound to the MMP13 promoter region and was demonstrated to upregulate MMP13 expression levels. Furthermore, FOSL1 knockdown inhibited DSS‑induced inflammation and barrier damage in HT29 cells via MMP13 downregulation. FOSL1 knockdown also ameliorated colonic injury, inflammation and barrier damage in the tissues of the UC mice model via MMP13 downregulation. Overall, FOSL1 knockdown was demonstrated to potentially ameliorate DSS‑induced inflammatory injury and protect the intestinal barrier integrity in the UC mice model via MMP13 downregulation.

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