ArticleCancer biology & therapy2014
Activation of p38-MAPK by CXCL4/CXCR3 axis contributes to p53-dependent intestinal apoptosis initiated by 5-fluorouracil.
Article in Cancer biology & therapy, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 41 citations in OpenAlex.
- The Protective Effects ofFood science & nutrition · 2025Article
- Platelet activation stimulates macrophages to enhance ulcerative colitis through PF4/CXCR3 signaling.International journal of molecular medicine · 2025Article
- CXCL10 Enhances Acid-Sensing Ion Channel Currents in Rat Dorsal Root.Molecular neurobiology · 2025Article
- Lentinan's effect on gut microbiota and inflammatory cytokines in 5-FU-induced mucositis mice.AMB Express · 2025Article
- CXCL4/CXCR3 axis regulates cardiac fibrosis by activating TGF-β1/Smad2/3 signaling in mouse viral myocarditis.Immunity, inflammation and disease · 2024Article
- Experimental Chemotherapy-Induced Mucositis: A Scoping Review Guiding the Design of Suitable Preclinical Models.International journal of molecular sciences · 2022Article
- Chemokines modulate glycan binding and the immunoregulatory activity of galectins.Communications biology · 2021Article
- Knockdown of TRIM9 attenuates irinotecan‑induced intestinal mucositis in IEC‑6 cells by regulating DUSP6 expression via the P38 pathway.Molecular medicine reports · 2021Article
- Perturbations in Endocytotic and Apoptotic Pathways Are Associated With Chemotherapy-Induced Nausea.Biological research for nursing · 2021Article
- Prophylactic photobiomodulation therapy using 660 nm diode laser for oral mucositis in paediatric patients under chemotherapy: 5-year experience from a Brazilian referral service.Lasers in medical science · 2020Article
- Systems biology analysis identifies molecular determinants of chemotherapy-induced diarrhoea.Journal of molecular medicine (Berlin, Germany) · 2020Article
- MicroRNA-135a Protects Against Ethanol-Induced Apoptosis in Neural Crest Cells and Craniofacial Defects in Zebrafish by Modulating the Siah1/p38/p53 Pathway.Frontiers in cell and developmental biology · 2020Article
- CXCR3 from chemokine receptor family correlates with immune infiltration and predicts poor survival in osteosarcoma.Bioscience reports · 2019Article
- The pathogenesis of mucositis: updated perspectives and emerging targets.Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer · 2019Review
- 5-Fluorouracil Induces Enteric Neuron Death and Glial Activation During Intestinal Mucositis via a S100B-RAGE-NFκB-Dependent Pathway.Scientific reports · 2019Article
- TMEM119 silencing inhibits cell viability and causes the apoptosis of gastric cancer SGC-7901 cells.Oncology letters · 2018Article
- Anti-CXCL4 monoclonal antibody accelerates telogen to anagen transition and attenuates apoptosis of the hair follicle in mice.Experimental and therapeutic medicine · 2017Article
- Up-regulation of Siah1 by ethanol triggers apoptosis in neural crest cells through p38 MAPK-mediated activation of p53 signaling pathway.Archives of toxicology · 2017Article
- Alteration of Gut Microbiota and Inflammatory Cytokine/Chemokine Profiles in 5-Fluorouracil Induced Intestinal Mucositis.Frontiers in cellular and infection microbiology · 2017Article
- p38MAPK and Chemotherapy: We Always Need to Hear Both Sides of the Story.Frontiers in cell and developmental biology · 2016Review
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Chemotherapy-induced mucositis (CIM) is a major does limiting side-effect of chemoagents such as 5-fluorouracil (5-FU). Molecules involved in this disease process are still not fully understood. We proposed that the homeostatically regulated genes during CIM may participate in the disease. A cluster of such genes were previously identified by expression gene-array from the mouse jejunum in 5-FU-induced mucositis model. Here, we report that CXCL4 is such a homeostatically regulated gene and serves as a new target for the antibody treatment of CIM. CXCL4 and its receptor CXCR3 were confirmed at both the gene and protein levels to be homeostatically regulated during 5-FU-induced mucositis. Using of CXCL4 neutralizing monoclonal antibody (CXCL4mab) decreased the incidence, severity, and duration of the chemotherapy-induced diarrhea, the major symptom of CIM, in a 5-FU mouse CIM model. Mechanistically, CXCL4mab reduced the apoptosis of the crypt epithelia by suppression of the 5-FU-induced expression of p53 and Bax through its receptor CXCR3. The downstream signaling pathway of CXCL4 in activation of the epithelial apoptosis was identified in an intestinal epithelial cell line (IEC-6). CXCL4 activated the phosphorylation of p38 MAPK, which mediated the stimulated expression of p53 and Bax, and resulted in the ultimate activation of Caspase-8, -9, and -3. Taken together, activation of CXCL4 expression by 5-FU in mice participates in 5-FU-induced intestinal mucositis through upregulation of p53 via activation of p38-MAPK, and CXCL4mab is potentially beneficial in preventing CIM in the intestinal tract.
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