Role of TRIM22 in ulcerative colitis and its underlying mechanisms

Ye,Bin; Lu,Zhongkai

doi:10.3892/mmr.2022.12765

Role of TRIM22 in ulcerative colitis and its underlying mechanisms

Authors:
- Bin Ye
- Zhongkai Lu
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Affiliations: Department of Gastroenterology, Hangzhou Hospital of Traditional Chinese Medicine, Hangzhou, Zhejiang 310000, P.R. China, Department of Gastroenterology, Suzhou Municipal Hospital, Suzhou Hospital Affiliated to Nanjing Medical University, Suzhou, Jiangsu 215001, P.R. China
Published online on: June 7, 2022 https://doi.org/10.3892/mmr.2022.12765
Article Number: 249
Copyright: © Ye 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 common chronic recurrent inflammatory disease, which seriously threatens human life and health. Therefore, the present study aimed to explore the role of tripartite motif‑containing (TRIM)22 in UC and its potential mechanism. C57BL/6 mice and HT‑29 cell models of UC were constructed using 2% dextran sulphate sodium (DSS). The protein and mRNA expression levels were detected by western blotting and reverse transcription‑quantitative PCR, respectively. Cell transfection was performed to overexpress Kruppel‑like factor 2 (KLF2), or knockdown KLF2, TRIM22 and TRIM30 expression. The levels of inflammatory factors were evaluated by enzyme‑linked immunosorbent assays. Cell Counting Kit‑8 and TUNEL staining assay were employed to assess cell viability and apoptosis. Dual‑luciferase reporter assay and chromatin immunoprecipitation assay were performed to determine the binding ability of the TRIM22 promoter to KLF2. The results revealed that DSS increased the expression levels of TRIM22 in HT‑29 cells and TRIM30 in mice. Short hairpin RNA (sh)‑TRIM30 could inhibit the NF‑κB pathway, and reduce the levels of TNF‑α, IL‑6 and IFN‑γ. Furthermore, KLF2 expression was downregulated in the cell model of UC, and the luciferase assay confirmed that the 3' untranslated region of TRIM22 was a direct target of KLF2. The ChIP assay also verified the binding of KLF2 with the TRIM22 promoter. Notably, knockdown of KLF2 reversed the enhancing effects of sh‑TRIM22 on the viability of DSS‑treated HT‑29 cells. In addition, compared with in the DSS + sh‑TRIM22 group, the protein expression levels of phosphorylated (p)‑NF‑κB and p‑IκBα were increased in the DSS + sh‑TRIM22 + sh‑KLF2 group, as were the levels of TNF‑α, IL‑6 and IFN‑γ. In conclusion, TRIM22 was upregulated in DSS‑induced HT‑29 cells. TRIM22 knockdown increased DSS‑induced HT‑29 cell viability and decreased apoptosis and inflammation; this was reversed by knockdown of KLF2. These findings suggested that TRIM22 may promote disease development through the NF‑κB signaling pathway in UC and could be inhibited by KLF2 transcription.

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