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Tumor necrosis factor receptor-associated factor 5 enhances perianal fistulizing Crohn's disease through
Xiaomei Sun1, Hairui Gao2, Lu Lu3
1Department of Colorectal Surgery, The Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Chinese Medicine, the First Clinical Medical College, Nanjing, Jiangsu, China.
Insights
Tumor necrosis factor receptor-associated factor 5 (TRAF5) drives perianal fistulizing Crohn's disease (PFCD) by promoting epithelial-mesenchymal transition (EMT). Reducing TRAF5 expression alleviates PFCD development and associated cellular changes.
Area of Science:
- Gastroenterology
- Molecular Biology
- Immunology
Background:
- Crohn's disease (CD) is a chronic inflammatory bowel condition with significant impact on quality of life.
- Perianal fistulizing CD (PFCD) is a common and challenging manifestation of CD.
- Understanding the molecular underpinnings of PFCD is crucial for improved management.
Purpose of the Study:
- To elucidate the molecular mechanisms driving PFCD.
- To identify potential biomarkers for PFCD.
- To investigate the role of TRAF5 in PFCD pathogenesis.
Main Methods:
- Transcriptome sequencing was employed to compare PFCD and control groups.
- Quantitative polymerase chain reaction (qPCR) and Western blot were used to detect gene and protein expression.
- Immunohistochemistry assessed protein levels of TRAF5, E-cadherin, SNAIL1, and vimentin.
- Cell proliferation and migration assays were performed after TRAF5 knockdown in HT-29 cells.
Main Results:
- Transcriptomic analysis revealed significant upregulation of TRAF5 in PFCD.
- Elevated mRNA levels of NF-κB and IL-13 were observed in PFCD.
- PFCD was associated with increased TRAF5, SNAIL1, and vimentin, and decreased E-cadherin, suggesting epithelial-mesenchymal transition (EMT).
- TRAF5 knockdown reduced cell proliferation and migration, inhibited NF-κB and IL-13, and promoted E-cadherin expression.
Conclusions:
- PFCD development is linked to EMT.
- TRAF5 is identified as a key gene in PFCD pathogenesis.
- TRAF5 drives PFCD progression through EMT, and its knockdown mitigates this process.
Objective:
Crohn's disease (CD) is a chronic inflammatory condition of the bowel that remarkably impairs a patient's quality of life and often has a poor prognosis. Perianal fistulizing CD (PFCD) is one of the most common parenteral symptoms of CD and a huge challenge for the management of this illness. This study aimed to elucidate the molecular mechanisms underlying PFCD and identify potential biomarkers to advance our understanding and management of this condition.
Material And Methods:
Transcriptome sequencing was performed using the control and PFCD groups to investigate the mechanisms of PFCD development. The expression of tumor necrosis factor receptor-associated factor 5 (TRAF5), nuclear factor-kappa B (NF-κB), and interleukin 13 (IL-13) messenger ribonucleic acid (mRNAs) was detected by quantitative polymerase chain reaction (qPCR). Pathological morphology was observed using hematoxylin and eosin staining. The expression of TRAF5, Epithelial Cadherin (E-cadherin), Snail family transcriptional repressor 1 (SNAIL1), and vimentin protein was detected by immunohistochemistry. Following the knockdown of TRAF5 in human tumor-29 (HT-29) cells, the effects on cell proliferation and migration were assessed using the cell counting kit-8 and Transwell assays. The expression levels of crucial markers were analyzed by qPCR, Western blot, and immunohistochemistry.
Results:
Transcriptomic sequencing revealed a significant upregulation of TRAF5 in the PFCD group, accompanied by elevated mRNA levels of NF-κB and IL-13 compared with those in the control group. In addition, the PFCD group exhibited increased expression of TRAF5, SNAIL, and vimentin and marked reduction in E-cadherin levels, indicating that PFCD may facilitate epithelial-mesenchymal transition (EMT). Knocking down TRAF5 in HT-29 cells reduced cell proliferation and migration; inhibited NF-κB and IL-13 mRNAs, SNAIL1, and vimentin levels; and promoted E-cadherin levels.
Conclusions:
The development of PFCD was associated with EMT, and TRAF5 was a key gene of PFCD. Knocking down TRAF5 alleviated the EMT promotion of PFCD, indicating that TRAF5 drove the development of PFCD through EMT.
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