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Updated: Jun 5, 2025
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Published on: October 19, 2013
THBS1 mediates hypoxia driven EndMT in pulmonary hypertension
Bingming Peng1,2,3, Yingzhen Zhou1,2,3, Xingmeng Fu1,2,3
1Department of Respiratory, Thoracic and Cardiac Surgery, Cardiovascular Medicine Children's Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders Chongqing China.
Thrombospondin 1 (THBS1) drives hypoxia-induced Endothelial to Mesenchymal Transition (EndMT) in pulmonary hypertension (PH). Inhibiting THBS1 reversed EndMT, offering new insights into PH pathophysiology for congenital heart disease patients.
Area of Science:
- Cardiovascular Biology
- Pulmonary Hypertension Pathophysiology
- Cellular Biology
Background:
- Long-term hypoxia contributes to pulmonary vascular remodeling in pediatric pulmonary hypertension (PH) associated with congenital heart disease (CHD).
- Endothelial to Mesenchymal Transition (EndMT) is a key pathological process in PH-related pulmonary vascular remodeling.
Purpose of the Study:
- To investigate the role of Thrombospondin 1 (THBS1) and Fibronectin 1 (FN1) in hypoxia-driven Endothelial to Mesenchymal Transition (EndMT) in pulmonary hypertension (PH).
- To explore THBS1 as a potential therapeutic target for reversing EndMT in PH.
Main Methods:
- Analysis of protein-protein interactions (Fibronectin 1 with Thrombospondin 1 and Transglutaminase 2) in pediatric PH patient samples.
- Utilized LungMAP CellCards and heatmaps to assess THBS1 and FN1 expression in human pulmonary artery endothelial cells (PAEC) and mouse lung tissues.
- Employed a SUHX-induced PH mice model and hypoxia-induced human PAEC for in vivo and in vitro studies on the relationship between THBS1 and EndMT.
Main Results:
- Observed significant elevation of THBS1 and FN1 in PH contexts.
- Demonstrated that hypoxia induces EndMT.
- Confirmed that inhibiting THBS1 effectively reverses EndMT in both in vivo and in vitro models, validating transcriptome findings.
Conclusions:
- Thrombospondin 1 (THBS1) plays a critical role in mediating hypoxia-driven Endothelial to Mesenchymal Transition (EndMT) in pulmonary hypertension (PH).
- THBS1 inhibition presents a promising strategy for reversing EndMT in PH.
- This research provides novel insights into the pathophysiology of PH, particularly in the context of congenital heart disease.
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