Academic Journal
Wilms Tumor 1-associated Protein Promotes Sepsis-induced Disseminated Intravascular Coagulation by Stabilizing Intercellular Adhesion Molecule 1 Via N6-methyladenosine Modification.
| Τίτλος: | Wilms Tumor 1-associated Protein Promotes Sepsis-induced Disseminated Intravascular Coagulation by Stabilizing Intercellular Adhesion Molecule 1 Via N6-methyladenosine Modification. |
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| Συγγραφείς: | Jia X; Department of ICU, The Second Nanning People's Hospital, Guangxi Zhuang Autonomous Region, Nanning, 530000, China. Jiaxinju2025@126.com.; Department of ICU, The Second Nanning People's Hospital, No. 13, Tancun Road, Jiangnan District, Nanning, Guangxi Zhuang Autonomous Region, 530000, China. Jiaxinju2025@126.com., Su T; Department of ICU, The Second Nanning People's Hospital, Guangxi Zhuang Autonomous Region, Nanning, 530000, China., Liang H; Department of ICU, The Second Nanning People's Hospital, Guangxi Zhuang Autonomous Region, Nanning, 530000, China. |
| Πηγή: | Cardiovascular drugs and therapy [Cardiovasc Drugs Ther] 2026 Aug; Vol. 40 (4), pp. 1271-1281. Date of Electronic Publication: 2025 Nov 25. |
| Τύπος έκδοσης: | Journal Article |
| Γλώσσα: | English |
| Στοιχεία περιοδικού: | Publisher: Kluwer Academic For The International Society For Cardiovascular Pharmacotherapy Country of Publication: United States NLM ID: 8712220 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1573-7241 (Electronic) Linking ISSN: 09203206 NLM ISO Abbreviation: Cardiovasc Drugs Ther Subsets: MEDLINE |
| Imprint Name(s): | Publication: Norwell Ma : Kluwer Academic For The International Society For Cardiovascular Pharmacotherapy Original Publication: [Norwell, MA] : Martinus Nijhoff Pub., [c1987- |
| Ιατρικοί όροι (MeSH): | Sepsis*/complications , Sepsis*/metabolism , Sepsis*/genetics , Sepsis*/blood , Sepsis*/chemically induced , Disseminated Intravascular Coagulation*/genetics , Disseminated Intravascular Coagulation*/etiology , Disseminated Intravascular Coagulation*/metabolism , Disseminated Intravascular Coagulation*/blood , RNA Splicing Factors*/metabolism , RNA Splicing Factors*/genetics , Cell Cycle Proteins*/metabolism , Cell Cycle Proteins*/genetics , Intercellular Adhesion Molecule-1*/metabolism , Intercellular Adhesion Molecule-1*/genetics , Adenosine*/analogs & derivatives , Adenosine*/metabolism , Blood Coagulation*, Human Umbilical Vein Endothelial Cells/metabolism ; Animals ; Humans ; Male ; Disease Models, Animal ; Rats, Sprague-Dawley ; Lipopolysaccharides ; RNA Methylation ; Rats |
| Περίληψη: | Background: Disseminated intravascular coagulation (DIC) is a life-threatening condition characterized by uncontrolled coagulation and systemic inflammation, often triggered by sepsis. Recent studies highlight the role of N6-methyladenosine (m6A) modification in regulating endothelial dysfunction and coagulation pathways. However, the specific role of Wilms tumor 1-associated protein (WTAP)-a component of the m6A methyltransferase complex-in sepsis-induced DIC remains poorly understood. Methods: HUVECs were stimulated with LPS to establish an in vitro inflammation model. WTAP expression was knocked down using shRNA, and its effects on intercellular adhesion molecule 1 (ICAM1) and tissue factor (TF) expression were analyzed via qPCR, Western blot, and RIP assays. The stability of ICAM1 mRNA was assessed using Actinomycin D treatment. An in vivo sepsis-induced DIC rat model was used to evaluate coagulation parameters, histopathological changes, and WTAP and ICAM1, TF expression in response to WTAP knockdown. Results: LPS stimulation significantly increased WTAP expression and m6A modification levels in HUVECs, leading to increased ICAM1 expression and enhanced TF activity. WTAP knockdown reduced ICAM1 and TF expression, as well as TF activity. RIP and mRNA stability assays confirmed that WTAP stabilizes ICAM1 mRNA via m6A modification. In the DIC rat model, WTAP knockdown improved coagulation parameters, reduced microthrombus formation in lung and kidney tissues, and inhibited the coagulation cascade. Conclusion: WTAP stabilizes ICAM1 mRNA via m6A modification, thereby increasing ICAM1 expression and enhancing TF activity in LPS-stimulated HUVECs. Knocking down WTAP in rats improves sepsis-induced DIC. (© 2025. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.) |
| Competing Interests: | Declarations. Ethics Approval: Not Applicable. Consent for Publication: Not Applicable. Conflict of interest: The authors declare that they have no conflict of interest. |
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| Contributed Indexing: | Keywords: Disseminated intravascular coagulation; ICAM1; M6A modification; Sepsis; WTAP |
| Substance Nomenclature: | 0 (WTAP protein, human) 0 (RNA Splicing Factors) 0 (Cell Cycle Proteins) 126547-89-5 (Intercellular Adhesion Molecule-1) K72T3FS567 (Adenosine) CLE6G00625 (N-methyladenosine) 0 (ICAM1 protein, human) 0 (Lipopolysaccharides) |
| Entry Date(s): | Date Created: 20251125 Date Completed: 20260721 Latest Revision: 20260721 |
| Update Code: | 20260722 |
| DOI: | 10.1007/s10557-025-07794-y |
| PMID: | 41288861 |
| Βάση Δεδομένων: | MEDLINE |
| ISSN: | 1573-7241 |
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| DOI: | 10.1007/s10557-025-07794-y |