STAT1-mediated induction of Ly6c-expressing macrophages are involved in the pathogenesis of an acute colitis model

Kii, Shuhei; Kitamura, Hiroyuki; Hashimoto, Shinichi; Ikeo, Kazuho; Ichikawa, Nobuki; Yoshida, Tadashi; Homma, Shigenori; Tanino, Mishie; Taketomi, Akinobu

doi:10.1007/s00011-022-01620-z

Cited by 3 publications

(2 citation statements)

References 60 publications

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“…Indeed, after administration of cpd 46 we noted an increase in clinical symptoms, and a non-significant effect on inflammatory markers, except for TNF-α. Usually, the dual inhibition of these 2 transcription factors, greatly involved in the colitis mechanism [ 24 , 25 ], is considered as a potential strategy to enhance anti-inflammatory activity. Thus, it was quite surprising that cpd 46, which acts on both STAT1 and STAT3, was less effective than cpd 23.…”

Section: Discussionmentioning

confidence: 99%

Comparison of a selective STAT3 inhibitor with a dual STAT3/STAT1 inhibitor using a dextran sulfate sodium murine colitis model: new insight into the debate on selectivity

Moulari

2024

aog

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Background Recent advances in the treatment of inflammatory bowel disease include antitumor necrosis factor antibodies and the Janus kinase inhibitor tofacitinib, approved for ulcerative colitis. Janus kinase recruits signal transducers and activators of transcriptions (STAT), which are promising targets in inflammatory bowel diseases. However few inhibitors have been evaluated, and their selectivity with respect to STAT1 and STAT3 remains controversial. Here, we investigated the therapeutic potential of a selective inhibitor vs. a non-selective, closely related compound, in a dextran sulfate sodium (DSS) murine colitis model. Methods Thirty Swiss/CD-1 male mice were used in this study. They were divided into a healthy control group, a colitis-DSS control group, a compound (cpd) 23-treated group, a cpd 46-treated group and an icariin-treated group. For the coadministration experiment with rutin, the cpd 46-treated group and the icariin-treated group were replaced by the oral rutin-treated group and the coadministration rutin/cpd 23-treated group. The effect of the tested inhibitors was also assessed by quantification of proinflammatory markers. Results The selective inhibitor had a significantly greater effect than the dual inhibitor on the disease activity index. We also noticed in curative treatment a significant decrease in the most abundant proinflammatory biomarker present in neutrophilic granulocytes, myeloperoxidase and on proinflammatory cytokines, including tumor necrosis factor-α, interferon-γ, interleukins -6 and -23, with a mild synergy with rutin, the glycoside of quercetin. Conclusion The current study shows how STAT3 selective inhibitors can exert a significant therapeutic effect in the treatment of experimental DSS-colitis.

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Section: Discussionmentioning

confidence: 99%

Comparison of a selective STAT3 inhibitor with a dual STAT3/STAT1 inhibitor using a dextran sulfate sodium murine colitis model: new insight into the debate on selectivity

Moulari

2024

aog

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“…Furthermore, a study employing an acute colitis model revealed significant improvements in disease state among STAT1-deficient mice in comparison to wild-type mice. Notably, the induction of highly expressed Ly6c cells in colorectal tissues was notably reduced in STAT1-deficient mice ( 48 ). Serpin Peptidase Inhibitor 1 (SERPINE1) has been identified as a potential new disease activity marker in IBD, which includes Crohn’s disease.…”

Section: Discussionmentioning

confidence: 99%

Identification of platelet-related subtypes and diagnostic markers in pediatric Crohn’s disease based on WGCNA and machine learning

Tang,

Huang,

Che

et al. 2024

Front. Immunol.

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BackgroundThe incidence of pediatric Crohn’s disease (PCD) is increasing worldwide every year. The challenges in early diagnosis and treatment of PCD persist due to its inherent heterogeneity. This study’s objective was to discover novel diagnostic markers and molecular subtypes aimed at enhancing the prognosis for patients suffering from PCD.MethodsCandidate genes were obtained from the GSE117993 dataset and the GSE93624 dataset by weighted gene co-expression network analysis (WGCNA) and differential analysis, followed by intersection with platelet-related genes. Based on this, diagnostic markers were screened by five machine learning algorithms. We constructed predictive models and molecular subtypes based on key markers. The models were evaluated using the GSE101794 dataset as the validation set, combined with receiver operating characteristic curves, decision curve analysis, clinical impact curves, and calibration curves. In addition, we performed pathway enrichment analysis and immune infiltration analysis for different molecular subtypes to assess their differences.ResultsThrough WGCNA and differential analysis, we successfully identified 44 candidate genes. Following this, employing five machine learning algorithms, we ultimately narrowed it down to five pivotal markers: GNA15, PIK3R3, PLEK, SERPINE1, and STAT1. Using these five key markers as a foundation, we developed a nomogram exhibiting exceptional performance. Furthermore, we distinguished two platelet-related subtypes of PCD through consensus clustering analysis. Subsequent analyses involving pathway enrichment and immune infiltration unveiled notable disparities in gene expression patterns, enrichment pathways, and immune infiltration landscapes between these subtypes.ConclusionIn this study, we have successfully identified five promising diagnostic markers and developed a robust nomogram with high predictive efficacy. Furthermore, the recognition of distinct PCD subtypes enhances our comprehension of potential pathogenic mechanisms and paves the way for future prospects in early diagnosis and personalized treatment.

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CCR2: A characteristic chemokine receptor in normal and pathological intestine

Yuan

2023

Cytokine

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STAT1-mediated induction of Ly6c-expressing macrophages are involved in the pathogenesis of an acute colitis model

Cited by 3 publications

References 60 publications

Comparison of a selective STAT3 inhibitor with a dual STAT3/STAT1 inhibitor using a dextran sulfate sodium murine colitis model: new insight into the debate on selectivity

Comparison of a selective STAT3 inhibitor with a dual STAT3/STAT1 inhibitor using a dextran sulfate sodium murine colitis model: new insight into the debate on selectivity

Identification of platelet-related subtypes and diagnostic markers in pediatric Crohn’s disease based on WGCNA and machine learning

CCR2: A characteristic chemokine receptor in normal and pathological intestine

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