ArticleJournal of biomedical science2022
Thrombin induces IL-8/CXCL8 expression by DCLK1-dependent RhoA and YAP activation in human lung epithelial cells.
Article in Journal of biomedical science, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed.
- DCLK1-dependent NF-κB activation mediates p-STAT3-induced osteoarthritis progression.Clinical and translational medicine · 2026Article
- DCLK1 mediates airway epithelial barrier disruption through NF-κB activation in severe asthma.Molecular medicine (Cambridge, Mass.) · 2026Article
- Doublecortin-like kinase 1 promotes fibroblast activation and fibrotic progression through Smad3 binding in idiopathic pulmonary fibrosis.Journal of biomedical science · 2026Article
- A mechanistic study of bisphenol a exposure on asthma through integrating clinical research, network toxicology, machine learning, and multi-omics.Frontiers in pharmacology · 2026Article
- Serine/threonine kinase 33 mediates thrombin-induced interleukin-8 release from human lung epithelial cells in severe asthma.Respiratory research · 2025Article
- Mechanism of action of M-XQLD treatment for asthma: role of STARD13 in Th17 suppression.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2025Article
- Review
- Doublecortin-like kinase 1 promotes stem cell-like properties through the Hippo-YAP pathway in prostate cancer.International journal of medical sciences · 2025Article
- Identification of Co-Diagnostic Genes and Potential Therapeutic Targets for Asthma and Sepsis Through Mendelian Randomization and Immune Infiltration Analysis.Journal of asthma and allergy · 2025Article
- Tumor-Activated Neutrophils Promote Lung Cancer Progression through the IL-8/PD-L1 Pathway.Current cancer drug targets · 2025Article
- Inhibition of acid-sensing receptor GPR4 attenuates neuronal ferroptosis via RhoA/YAP signaling in a rat model of subarachnoid hemorrhage.Free radical biology & medicine · 2024Article
- IL-8 (CXCL8) Correlations with Psychoneuroimmunological Processes and Neuropsychiatric Conditions.Journal of personalized medicine · 2024Review
- scRNA-Seq: First Atlas and Cellular Landscape of Lacrimal Sac: Implications in Primary Acquired Nasolacrimal Duct Obstruction Pathogenesis.Investigative ophthalmology & visual science · 2024Article
- Role of DCLK1/Hippo pathway in type II alveolar epithelial cells differentiation in acute respiratory distress syndrome.Molecular medicine (Cambridge, Mass.) · 2023Article
- Article
- FAP promotes metastasis and chemoresistance via regulating YAP1 and macrophages in mucinous colorectal adenocarcinoma.iScience · 2023Article
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Authors and funding
6 authors.
Funding
Abstract
backgroundDoublecortin-like kinase 1 (DCLK1) has been recognized as a marker of cancer stem cell in several malignancies. Thrombin is crucial in asthma severity as it can promote IL-8/CXCL8 production in lung epithelial cells, which is a potent chemoattractant for neutrophils. However, the pathologic role of DCLK1 in asthma and its involvement in thrombin-stimulated IL-8/CXCL8 expression remain unknown.
methodsIL-8/CXCL8, thrombin, and DCLK1 expression were observed in the lung tissues of severe asthma patients and ovalbumin (OVA)-induced asthmatic mice model. A549 and BEAS-2B cells were either pretreated with inhibitors or small interfering RNAs (siRNAs) before being treated with thrombin. IL-8/CXCL8 expression and the molecules involved in signaling pathway were performed using ELISA, luciferase activity assay, Western blot, or ChIP assay.
resultsIL-8/CXCL8, thrombin, and DCLK1 were overexpressed in the lung tissues of severe asthma patients and ovalbumin (OVA)-induced asthmatic mice model. Our in vitro study found that DCLK siRNA or LRKK2-IN-1 (DCLK1 inhibitor) attenuated IL-8/CXCL8 release after thrombin induction in A549 and BEAS-2B cells. Thrombin activated DCLK1, RhoA, and YAP in a time-dependent manner, in which DCLK1 siRNA inhibited RhoA and YAP activation. YAP was dephosphorylated on the Ser127 site after thrombin stimulation, resulting in YAP translocation to the nucleus from the cytosol. DCLK1, RhoA and YAP activation following thrombin stimulation were inhibited by U0126 (ERK inhibitor). Moreover, DCLK1 and YAP siRNA inhibited κB-luciferase activity. Thrombin stimulated the recruitment of YAP and p65 to the NF-κB site of the IL-8/CXCL8 promoter and was inhibited by DCLK1 siRNA.
conclusionsThrombin activates the DCLK1/RhoA signaling pathway, which promotes YAP activation and translocation to the nucleus from the cytosol, resulting in YAP/p65 formation, and binding to the NF-κB site, which enhances IL-8/CXCL8 expression. DCLK1 might be essential in thrombin-stimulated IL-8/CXCL8 expression in asthmatic lungs and indicates a potential therapeutic strategy for severe asthma treatment.
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