Evidence map›Paper›PMID 36369000›Full record

ArticleJournal of biomedical science2022

Thrombin induces IL-8/CXCL8 expression by DCLK1-dependent RhoA and YAP activation in human lung epithelial cells.

Fara Silvia Yuliani, Jing-Yun Chen, Wen-Hao Cheng, Heng-Ching Wen, Bing-Chang Chen, Chien-Huang Lin

Abstract read
In one paragraph

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.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

16 citing papers in PubMed.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Article
  6. 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.] · 2025
    Article
  7. Review
  8. Article
  9. Article
  10. Article
  11. Article
  12. Review
  13. Article
  14. Article
  15. Article
  16. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors.

Fara Silvia YulianiInternational Graduate Program in Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.
Jing-Yun ChenGraduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei, Taiwan.
Wen-Hao ChengSchool of Respiratory Therapy College of Medicine, Taipei Medical University, Taipei, Taiwan.
Heng-Ching WenSchool of Respiratory Therapy College of Medicine, Taipei Medical University, Taipei, Taiwan.
Bing-Chang ChenGraduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei, Taiwan. bcchen@tmu.edu.tw.
Chien-Huang LinGraduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei, Taiwan. chlin@tmu.edu.tw.ORCID http://orcid.org/0000-0002-0916-8737

Funding

Ministry of Science and Technology, Taiwan MOST-109-2320-B-038-024-MY3Ministry of Science and Technology, Taiwan MOST-109-2320-B-038 -026 -MY3
6 · The paper itself

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.

Indexed as

AsthmaInterleukin-8AnimalsDoublecortin-Like KinasesEpithelial CellsHumansLuciferasesLungMiceNF-kappa BOvalbuminPhosphorylationProtein Serine-Threonine KinasesrhoA GTP-Binding ProteinRNA, Small InterferingThrombinDCLK1 protein, humanDoublecortin-Like KinasesInterleukin-8LuciferasesNF-kappa BOvalbuminProtein Serine-Threonine KinasesrhoA GTP-Binding ProteinRHOA protein, humanRNA, Small InterferingThrombinDCLK1Lung epithelial cellsRhoASevere asthmaYAP

Identifiers

PMID36369000
PMCPMC9650896

What Socratic holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.