PUBLICATION
Xanthotoxin, a novel inducer of platelet formation, promotes thrombocytopoiesis via IL-1R1 and MEK/ERK signaling
- Authors
- Lai, J., Li, Y., Ran, M., Huang, Q., Huang, F., Zhu, L., Wu, Y., Zou, W., Xie, X., Tang, Y., Yang, F., Wu, A., Ge, G., Wu, J.
- ID
- ZDB-PUB-230509-42
- Date
- 2023
- Source
- Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 163: 114811114811 (Journal)
- Registered Authors
- Keywords
- MEK/ERK, Megakaryocyte differentiation, Platelets, Thrombocytopenia, Xanthotoxin
- MeSH Terms
-
- Animals
- Blood Platelets
- Megakaryocytes
- Methoxsalen/pharmacology
- Mice
- Mitogen-Activated Protein Kinase Kinases/metabolism
- Signal Transduction
- Thrombocytopenia*/drug therapy
- Thrombopoiesis*
- Transcription Factors/metabolism
- Zebrafish/metabolism
- PubMed
- 37156117 Full text @ Biomed. Pharmacother.
Citation
Lai, J., Li, Y., Ran, M., Huang, Q., Huang, F., Zhu, L., Wu, Y., Zou, W., Xie, X., Tang, Y., Yang, F., Wu, A., Ge, G., Wu, J. (2023) Xanthotoxin, a novel inducer of platelet formation, promotes thrombocytopoiesis via IL-1R1 and MEK/ERK signaling. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie. 163:114811114811.
Abstract
Background Thrombocytopenia is a common hematological disease caused by many factors. It usually complicates critical diseases and increases morbidity and mortality. The treatment of thrombocytopenia remains a great challenge in clinical practice, however, its treatment options are limited. In this study, the active monomer xanthotoxin (XAT) was screened out to explore its medicinal value and provide novel therapeutic strategies for the clinical treatment of thrombocytopenia.
Methods The effects of XAT on megakaryocyte differentiation and maturation were detected by flow cytometry, Giemsa and phalloidin staining. RNA-seq identified differentially expressed genes and enriched pathways. The signaling pathway and transcription factors were verified through WB and immunofluorescence staining. Tg (cd41: eGFP) transgenic zebrafish and mice with thrombocytopenia were used to evaluate the biological activity of XAT on platelet formation and the related hematopoietic organ index in vivo.
Results XAT promoted the differentiation and maturation of Meg-01 cells in vitro. Meanwhile, XAT could stimulate platelet formation in transgenic zebrafish and recover platelet production and function in irradiation-induced thrombocytopenia mice. Further RNA-seq prediction and WB verification revealed that XAT activates the IL-1R1 target and MEK/ERK signaling pathway, and upregulates the expression of transcription factors related to the hematopoietic lineage to promote megakaryocyte differentiation and platelet formation.
Conclusion XAT accelerates megakaryocyte differentiation and maturation to promote platelet production and recovery through triggering IL-1R1 and activating the MEK/ERK signaling pathway, providing a new pharmacotherapy strategy for thrombocytopenia.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping