Evidence map›Paper›PMID 39741411›Full record

ArticleMolecular therapy : the journal of the American Society of Gene Therapy2025

Impaired megakaryopoiesis due to aberrant macrophage polarization via BTK/Rap1/NF-κB pathway in sepsis-induced thrombocytopenia.

Ziyan Zhang, Meng Zhou, Yaqiong Tang, Jiaqian Qi, Xiaoyan Xu, Peng Wang, Haohao Han, Tingting Pan, Xiaofei Song, Shuhui Jiang and 8 more

Abstract read
In one paragraph

Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed, 1 pooled it
–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

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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

10 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Structural Characterization of Acidic Polysaccharides fromAntioxidants (Basel, Switzerland) · 2026
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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

18 authors.

Ziyan ZhangNational Clinical Research Center for Hematologic Diseases, Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, China; Institute of Blood and Marrow Transplantation, Collaborative Innovation Center of Hematology, Soochow University, Suzhou, Jiangsu 215006, China; Department of Hematology, Affiliated Kunshan Hospital of Jiangsu University, 566 East Qianjin Road, Suzhou, Jiangsu 215300, China.
Meng ZhouNational Clinical Research Center for Hematologic Diseases, Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, China; Institute of Blood and Marrow Transplantation, Collaborative Innovation Center of Hematology, Soochow University, Suzhou, Jiangsu 215006, China; Key Laboratory of Thrombosis and Hemostasis of Ministry of Health, Suzhou, Jiangsu 215006, China; State Key Laboratory of Radiation Medicine and Protection, Soochow University, Suzhou, Jiangsu 215006, China.
Yaqiong TangNational Clinical Research Center for Hematologic Diseases, Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, China; Institute of Blood and Marrow Transplantation, Collaborative Innovation Center of Hematology, Soochow University, Suzhou, Jiangsu 215006, China; Key Laboratory of Thrombosis and Hemostasis of Ministry of Health, Suzhou, Jiangsu 215006, China; State Key Laboratory of Radiation Medicine and Protection, Soochow University, Suzhou, Jiangsu 215006, China.
Jiaqian QiNational Clinical Research Center for Hematologic Diseases, Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, China; Institute of Blood and Marrow Transplantation, Collaborative Innovation Center of Hematology, Soochow University, Suzhou, Jiangsu 215006, China; Key Laboratory of Thrombosis and Hemostasis of Ministry of Health, Suzhou, Jiangsu 215006, China; State Key Laboratory of Radiation Medicine and Protection, Soochow University, Suzhou, Jiangsu 215006, China.
Xiaoyan XuNational Clinical Research Center for Hematologic Diseases, Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, China; Institute of Blood and Marrow Transplantation, Collaborative Innovation Center of Hematology, Soochow University, Suzhou, Jiangsu 215006, China; Key Laboratory of Thrombosis and Hemostasis of Ministry of Health, Suzhou, Jiangsu 215006, China; State Key Laboratory of Radiation Medicine and Protection, Soochow University, Suzhou, Jiangsu 215006, China.
Peng WangNational Clinical Research Center for Hematologic Diseases, Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, China; Institute of Blood and Marrow Transplantation, Collaborative Innovation Center of Hematology, Soochow University, Suzhou, Jiangsu 215006, China; Key Laboratory of Thrombosis and Hemostasis of Ministry of Health, Suzhou, Jiangsu 215006, China; State Key Laboratory of Radiation Medicine and Protection, Soochow University, Suzhou, Jiangsu 215006, China.
Haohao HanNational Clinical Research Center for Hematologic Diseases, Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, China; Institute of Blood and Marrow Transplantation, Collaborative Innovation Center of Hematology, Soochow University, Suzhou, Jiangsu 215006, China.
Tingting PanNational Clinical Research Center for Hematologic Diseases, Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, China; Institute of Blood and Marrow Transplantation, Collaborative Innovation Center of Hematology, Soochow University, Suzhou, Jiangsu 215006, China; Key Laboratory of Thrombosis and Hemostasis of Ministry of Health, Suzhou, Jiangsu 215006, China; State Key Laboratory of Radiation Medicine and Protection, Soochow University, Suzhou, Jiangsu 215006, China.
Xiaofei SongNational Clinical Research Center for Hematologic Diseases, Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, China; Institute of Blood and Marrow Transplantation, Collaborative Innovation Center of Hematology, Soochow University, Suzhou, Jiangsu 215006, China.
Shuhui JiangNational Clinical Research Center for Hematologic Diseases, Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, China; Institute of Blood and Marrow Transplantation, Collaborative Innovation Center of Hematology, Soochow University, Suzhou, Jiangsu 215006, China.
Xueqian LiNational Clinical Research Center for Hematologic Diseases, Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, China; Institute of Blood and Marrow Transplantation, Collaborative Innovation Center of Hematology, Soochow University, Suzhou, Jiangsu 215006, China.
Chengyuan GuNational Clinical Research Center for Hematologic Diseases, Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, China; Institute of Blood and Marrow Transplantation, Collaborative Innovation Center of Hematology, Soochow University, Suzhou, Jiangsu 215006, China; Key Laboratory of Thrombosis and Hemostasis of Ministry of Health, Suzhou, Jiangsu 215006, China; State Key Laboratory of Radiation Medicine and Protection, Soochow University, Suzhou, Jiangsu 215006, China.
Zhenzhen YaoNational Clinical Research Center for Hematologic Diseases, Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, China; Institute of Blood and Marrow Transplantation, Collaborative Innovation Center of Hematology, Soochow University, Suzhou, Jiangsu 215006, China.
Qixiu HouNational Clinical Research Center for Hematologic Diseases, Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, China; Institute of Blood and Marrow Transplantation, Collaborative Innovation Center of Hematology, Soochow University, Suzhou, Jiangsu 215006, China.
Mengting GuoNational Clinical Research Center for Hematologic Diseases, Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, China; Institute of Blood and Marrow Transplantation, Collaborative Innovation Center of Hematology, Soochow University, Suzhou, Jiangsu 215006, China.
Siyi LuNational Clinical Research Center for Hematologic Diseases, Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, China; Institute of Blood and Marrow Transplantation, Collaborative Innovation Center of Hematology, Soochow University, Suzhou, Jiangsu 215006, China.
Depei WuNational Clinical Research Center for Hematologic Diseases, Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, China; Institute of Blood and Marrow Transplantation, Collaborative Innovation Center of Hematology, Soochow University, Suzhou, Jiangsu 215006, China; Key Laboratory of Thrombosis and Hemostasis of Ministry of Health, Suzhou, Jiangsu 215006, China; State Key Laboratory of Radiation Medicine and Protection, Soochow University, Suzhou, Jiangsu 215006, China.
Yue HanNational Clinical Research Center for Hematologic Diseases, Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, China; Institute of Blood and Marrow Transplantation, Collaborative Innovation Center of Hematology, Soochow University, Suzhou, Jiangsu 215006, China; Key Laboratory of Thrombosis and Hemostasis of Ministry of Health, Suzhou, Jiangsu 215006, China; State Key Laboratory of Radiation Medicine and Protection, Soochow University, Suzhou, Jiangsu 215006, China. Electronic address: hanyue@suda.edu.cn.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Sepsis-induced thrombocytopenia (SIT) is a widely accepted predictor of poor prognosis during sepsis, while the mechanism of SIT remains elusive. In this study, we revealed that SIT patients and septic mice exhibited higher levels of pro-inflammatory macrophages and phosphorylated Bruton's tyrosine kinase (p-BTK) expression in macrophages, which were closely correlated with platelet counts. Treatment with the BTK inhibitor BGB-3111 in SIT mice resulted in enhanced production of megakaryocytes and platelets. Depletion of macrophages in SIT mice and coculture experiments further confirmed the critical role of macrophages in the improvement of platelet count induced by BGB-3111. By performing single-cell RNA sequencing on bone marrow-derived cells from SIT mice, we not only confirmed the connection between macrophages and megakaryocytes influenced by BTK but also identified a potential mediation through the Rap1 signaling pathway in macrophages. Subsequent experiments in macrophages demonstrated that inhibition of BTK signaling impeded the pro-inflammatory polarization of macrophages by targeting the Rap1/NF-κB signaling pathway. In conclusion, our study highlights the crucial role of macrophages in SIT, and inhibiting phosphorylation of BTK in macrophages may alleviate SIT through the Rap1/NF-κB signaling pathway.

Indexed as

Agammaglobulinaemia Tyrosine KinaseMacrophagesNF-kappa Brap1 GTP-Binding ProteinsSepsisSignal TransductionThrombocytopeniaThrombopoiesisAnimalsBlood PlateletsDisease Models, AnimalFemaleHumansMaleMegakaryocytesMiceAgammaglobulinaemia Tyrosine KinaseBTK protein, humanBtk protein, mouseNF-kappa Brap1 GTP-Binding ProteinsBTKmacrophagesmegakaryocytessepsisthrombocytopenia

Identifiers

PMID39741411
PMCPMC11997490

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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 OpenQuestion graph.