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Dipeptidyl peptidase 4: A predictor of ferroptosis in ulcerative colitis.
- Source :
-
The journal of gene medicine [J Gene Med] 2024 Oct; Vol. 26 (10), pp. e3742. - Publication Year :
- 2024
-
Abstract
- Background: With its rapidly increasing incidence and prevalence, ulcerative colitis (UC) has become a major global health challenge. Recent evidence suggests that ferroptosis plays a significant role in the development of UC. However, the relationship between ferroptosis and the progression of UC needs to be extensively studied.<br />Methods: The differentially expressed genes in UC patients were screened from the GEO database. The ferroptosis-related genes were obtained from FErrDB and GeneCards. The UC subtypes were identified with the R package "CancerSubtype" and evaluated with consensus clustering (CC) to identify gene expression patterns in patients with UC. The key genes were detected with qRT-PCR, Western blot, and immunohistochemistry in vitro and in vivo models. Ferroptosis was identified with western blotting on ferrotic-associated proteins and staining on Fe <superscript>2+</superscript> with commercial FerroOrange kits.<br />Results: Dipeptidyl peptidase 4 (DPP4), also known as CD26, is a potential biomarker for ferroptosis in UC patients. Transcriptome sequencing data showed a positive correlation between decreased DPP4 expression and proinflammatory cytokines such as TNF-α, IL-6, and IL-β, as well as immune cell infiltration in the colon tissues of UC patients. Furthermore, DPP4 was strongly associated with ferroptosis biomarkers, particularly in Subtype 2 of UC. Interestingly, our study also found that DPP4 expression was significantly reduced in RSL3-treated ferroptotic intestinal epithelial cells, more so than in LPS-treated cell models. Inhibition of DPP4 had a significant impact on the expression of ferroptotic biomarkers. Additionally, DPP4 expression was decreased in the colon tissues of DSS-treated mice, and the ferroptosis inhibitor Ferritin-1 effectively counteracted the effects of DSS on immune cell infiltration, colon length, and DPP4 expression.<br />Conclusions: DPP4 can serve as a biomarker for ferroptosis in the diagnosis and management of UC.<br /> (© 2024 John Wiley & Sons Ltd.)
- Subjects :
- Humans
Mice
Animals
Cytokines metabolism
Gene Expression Profiling
Disease Models, Animal
Male
Transcriptome
Ferroptosis genetics
Colitis, Ulcerative genetics
Colitis, Ulcerative pathology
Colitis, Ulcerative metabolism
Dipeptidyl Peptidase 4 metabolism
Dipeptidyl Peptidase 4 genetics
Biomarkers
Subjects
Details
- Language :
- English
- ISSN :
- 1521-2254
- Volume :
- 26
- Issue :
- 10
- Database :
- MEDLINE
- Journal :
- The journal of gene medicine
- Publication Type :
- Academic Journal
- Accession number :
- 39343840
- Full Text :
- https://doi.org/10.1002/jgm.3742