IL-9 promotes the development of deep venous thrombosis by facilitating platelet function
Open accessAbstract
The development of deep venous thrombosis (DVT) is a sterile inflammatory process related to cytokines, such as interleukin (IL)-6 or IL-17. IL-9 is a cytokine involved in many inflammatory diseases, including cystic fibrosis, ulcerative colitis, psoriasis and psoriatic arthritis. However, it remains unknown whether IL-9 is related to DVT. In this study, we characterized the role and mechanism of IL-9 in DVT. Analysis of the data of patients with and without DVT revealed that stasis, venous surgery as well as elevated IL-9 and sP-selectin levels were related to the development of DVT. We also showed for the first time that IL-9 receptor was expressed in mouse platelets, and it dramatically promoted the aggregation rate and expression of P-selectin (CD62P) in the presence of adenosine diphosphate, but otherwise exhibited no effect on platelets. This study also revealed that Janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) signalling pathway, not phosphoinositide 3-kinase/AKT pathway, was involved in the process. We also showed in a mouse model of stasis that the thrombus size (weight and length) and CD62P expression in the thrombus were higher and lower in the IL-9 group and IL-9 antibody group, respectively, than in the control group. All these findings indicated that IL-9 facilitated platelet function through the JAK2/STAT3 pathway, thus promoting the development of DVT.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
IL-9 through a JAK2/STAT3 signaling pathway facilitates platelet function and promotes development of deep venous thrombosis.
“IL-9 through a JAK2/STAT3 signaling pathway facilitated platelet function and promoted development of deep venous thrombosis”
From Targeting Janus Kinases and Signal Transducer and Activator of Transcription 3 To Treat Inflammation, Fibrosis, and Cancer: Rationale, Progress, and Caution (2020) · cites this paper as Feng et al., 2018
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
No references could be resolved yet.
Research works printed but not linked: 20
- Law Y, Chan YC, Cheng SWK. Epidemiological updates of venous thromboembolism in a Chinese population. Asian J Surg 2018;41 (02):176-182
- Dewyer NA, El-Sayed OM, Luke CE, et al. Divergent effects of Tlr9 deletion in experimental late venous thrombosis resolution and vein wall injury. Thromb Haemost 2015;114(05):1028-1037
- Zhang S, Yuan J, Yu M, et al. IL-17A facilitates platelet function through the ERK2 signaling pathway in patients with acute coronary syndrome. PLoS One 2012;7(07):e40641
- Yuan J, Ding PW, Yu M, et al. IL-17 induces MPTP opening through ERK2 and P53 signaling pathway in human platelets. J Huazhong Univ Sci Technolog Med Sci 2015;35(05):679-683
- Nowak EC, Weaver CT, Turner H, et al. IL-9 as a mediator of Th17- driven inflammatory disease. J Exp Med 2009;206(08):1653-1660
- Singh TP, Schön MP, Wallbrecht K, Gruber-Wackernagel A, Wang XJ, Wolf P. Involvement of IL-9 in Th17-associated inflammation and angiogenesis of psoriasis. PLoS One 2013;8(01):e51752
- Han JS, Park TS, Cho SY, Joh JH, Ahn HJ. Increased mean platelet volume and mean platelet volume/platelet count ratio in Korean patients with deep vein thrombosis. Platelets 2013;24(08):590-593
- Panuganti S, Schlinker AC, Lindholm PF, Papoutsakis ET, Miller WM. Three-stage ex vivo expansion of high-ploidy megakaryo- cytic cells: toward large-scale platelet production. Tissue Eng Part A 2013;19(7-8):998-1014
- Simanek R, Vormittag R, Ay C, et al. High platelet count associated with venous thromboembolism in cancer patients: results from the Vienna Cancer and Thrombosis Study (CATS). J Thromb Hae- most 2010;8(01):114-120
- Zhang W, Tang T, Nie D, et al. IL-9 aggravates the development of atherosclerosis in ApoE-/-mice. Cardiovasc Res 2015;106(03): 453-464
- Mosevoll KA, Lindãs R, Tvedt THA, Bruserud Ø, Reikvam H. Altered plasma levels of cytokines, soluble adhesion molecules and matrix metalloproteases in venous thrombosis. Thromb Res 2015;136(01):30-39 12
- González-Ordóñez AJ, Fernández-Carreira JM, Fernández-Alvarez CR, et al. The concentrations of soluble vascular cell adhesion molecule-1 and lipids are independently associated with venous thromboembolism. Haematologica 2003;88(09):1035-1043 13
- Antonopoulos CN, Sfyroeras GS, Kakisis JD, Moulakakis KG, Liapis CD. The role of soluble P selectin in the diagnosis of venous thromboembolism. Thromb Res 2014;133(01):17-24
- Hou H, Ge Z, Ying P, et al. Biomarkers of deep venous thrombosis. J Thromb Thrombolysis 2012;34(03):335-346
- Vandy FC, Stabler C, Eliassen AM, et al. Soluble P-selectin for the diagnosis of lower extremity deep venous thrombosis. J Vasc Surg Venous Lymphat Disord 2013;1(02):117-1125
- Brill A, Fuchs TA, Chauhan AK, et al. von Willebrand factor- mediated platelet adhesion is critical for deep vein thrombosis in mouse models. Blood 2011;117(04):1400-1407
- Demoulin JB, Van Snick J, Renauld JC. Interleukin-9 (IL-9) induces cell growth arrest associated with sustained signal transducer and activator of transcription activation in lymphoma cells overexpres- sing the IL-9 receptor. Cell Growth Differ 2001;12(03):169-174
- Lu WJ, Lin KC, Huang SY, et al. Role of a Janus kinase 2-dependent signaling pathway in platelet activation. Thromb Res 2014;133 (06):1088-1096
- Tibbles HE, Vassilev A, Wendorf H, et al. Role of a JAK3-dependent biochemical signaling pathway in platelet activation and aggre- gation. J Biol Chem 2001;276(21):17815-17822
- Holinstat M, Preininger AM, Milne SB, Hudson WJ, Brown HA, Hamm HE. Irreversible platelet activation requires protease- activated receptor 1-mediated signaling to phosphatidylinositol phosphates. Mol Pharmacol 2009;76(02):301-313
Cited by
Sorted by citations
Bharadwaj, U., Kasembeli, M. M., Robinson, P., & Tweardy, D. J. (2020) · Pharmacological Reviews · doi:10.1124/pr.119.018440 · Cited by 314 · see citing works
- Authors
- Feng, Y., Yu, M., Zhu, F., Zhang, S., Ding, P., & Wang, M.
- Affiliations
- Wuhan Union Hospital (CN)
- Venue
- Thrombosis and Haemostasis
- Publisher
- Georg Thieme Verlag KG
- Published
- 2018-10-09
- Volume
- 118
- Issue
- 11
- Pages
- 1885-1894
- ISSN
- 0340-6245 (ISSN-L)
- 2567-689X
- OpenAlex
- W2898082547
- Cited by
- 26
- References
- 0
- Citations by year
- 2025: 3 · 2024: 2 · 2023: 6 · 2022: 3 · 2021: 1 · 2020: 11
- FWCI
- 2.15
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Thrombosis and Haemostasis (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Natural Science Foundation of China (81370425)
- Topics
- Health Sciences › Medicine › Hematology › Platelet Disorders and Treatments
- Health Sciences › Medicine › Hematology › Blood Coagulation and Thrombosis Mechanisms
- Health Sciences › Medicine › Internal Medicine › Venous Thromboembolism Diagnosis and Management
- Keywords
- IL-9, deep vein thrombosis, platelet function, platelet aggregation, P-selectin, IL-9 receptor, JAK2/STAT3 signaling, venous stasis, sterile inflammation, cytokines, thrombus formation
- MeSH terms
- Animals, Blood Platelets, Cells, Cultured, Humans, Male, Mice, Inbred BALB C, Platelet Aggregation, Signal Transduction, Interleukin-9, Disease Progression, P-Selectin, Antibodies, Blocking, Venous Thrombosis, STAT3 Transcription Factor, Mice, Janus Kinase 2, Receptors, Interleukin-9
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review