Ginsenoside Rg1 reduces endothelial cell injury in transplant-associated thromboticmicroangiopathy by regulating the expression of HIF-1α
Abstract
PurposeTransplant-Associated Thromboticmicroangiopathy (TA-TMA) is a common complication after hematopoietic stem cell transplantation (HSCT) with poor prognosis. This study aimed to explore the role and the regulation of Hypoxia-inducible factor-1α (HIF-1α) in TA-TMA. In addition, the effect of Ginsenoside Rg1 on TA-TMA endothelial cells was also explored.MethodWe constructed a TA-TMA endothelial cell model using plasma from TA-TMA patients. A TA-TMA mouse model was successfully constructed by upregulating the expression of HIF-1α using Dimethyloxallyl Glycine(DMOG) in the HSCT mice. AKT inhibitor MK2206 and STAT3 inhibitor stattic were applied to TA-TMA endothelial cells, and the expression of AKT/STAT3/HIF-1α axis was detected. Endothelial cells were divided into control group, TA-TMA group and TA-TMA+Rg1 group. The proliferation, apoptosis and related proteins expression of endothelial cells were detected.ResultsA-TMA plasma leaded to the toxicity of endothelial cells. The expression of p-AKT, p-STAT3, and HIF-1α/Plasminogen Activator Inhibitor-1 (PAI-1) was significantly increased in TA-TMA endothelial cell model. The expression of p-STAT3 and HIF-1α was significantly reduced when MK2206 was used. The expression of HIF-1α was significantly reduced when stattic was used. Rg1 reduced the toxicity of TA-TMA endothelial cells, as well as significantly reducing the expression of both HIF-1α and PAI-1. Furthermore, Rg1 also reduced the expression of AKT/STAT3/HIF-1α pathway.ConclusionThe expression of HIF-1α/PAI-1 was significantly increased in TA-TMA cellular and animal models. The AKT/STAT3/HIF-1α pathway was active in TA-TMA endothelial cells. Rg1 reduced the toxicity of TA-TMA endothelial cells, especially reducing the expression of HIF-1α and PAI-1.
Related
- Endothelial c-Maf prevents MASLD-like liver fibrosis by regulating chromatin accessibility to suppress pathogenic microvascular cell subsets
- A Reproducible Pre-Transplant γδ T-cell Effector Signature Reveals Immune-Metabolic Programs Associated with Kidney Allograft Rejection
- Pre-transplant whole blood transcriptomic profiling identifies mRNAs linked to cirrhosis-associated immune dysfunction as candidate predictors of clinical outcomes after liver transplantation: an exploratory study
- A recurrent cancer-associated fibroblast/TGF-beta/endothelial barrier direction is associated with immune exclusion and checkpoint resistance in bladder cancer: a public multi-cohort transcriptomic study
- The Alzheimer's Disease-associated gene CD2AP regulates permeability of endothelial cells and transendothelial migration of immune cells
BibTeX
@article{wang2026ginsenoside,
title = {{Ginsenoside Rg1 reduces endothelial cell injury in transplant-associated thromboticmicroangiopathy by regulating the expression of HIF-1α}},
author = {Manzhi Wang and Tao Sun and Hai Zhao and Peng Gao and Ying Gao and Guoxia Zhang and Xiaoqing Yang and Jianzhuang Guo and Ju Liu},
journal = {Frontiers in Immunology},
year = {2026},
month = nov,
doi = {10.3389/fimmu.2026.1764090},
url = {https://www.frontiersin.org/articles/10.3389/fimmu.2026.1764090},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Ginsenoside Rg1 reduces endothelial cell injury in transplant-associated thromboticmicroangiopathy by regulating the expression of HIF-1α
AU - Manzhi Wang
AU - Tao Sun
AU - Hai Zhao
AU - Peng Gao
AU - Ying Gao
AU - Guoxia Zhang
AU - Xiaoqing Yang
AU - Jianzhuang Guo
AU - Ju Liu
PY - 2026
DA - 2026/11/02
JO - Frontiers in Immunology
DO - 10.3389/fimmu.2026.1764090
UR - https://www.frontiersin.org/articles/10.3389/fimmu.2026.1764090
AB - PurposeTransplant-Associated Thromboticmicroangiopathy (TA-TMA) is a common complication after hematopoietic stem cell transplantation (HSCT) with poor prognosis. This study aimed to explore the role and the regulation of Hypoxia-inducible factor-1α (HIF-1α) in TA-TMA. In addition, the effect of Ginsenoside Rg1 on TA-TMA endothelial cells was also explored.MethodWe constructed a TA-TMA endothelial cell model using plasma from TA-TMA patients. A TA-TMA mouse model was successfully constructed by upregulating the expression of HIF-1α using Dimethyloxallyl Glycine(DMOG) in the HSCT mice. AKT inhibitor MK2206 and STAT3 inhibitor stattic were applied to TA-TMA endothelial cells, and the expression of AKT/STAT3/HIF-1α axis was detected. Endothelial cells were divided into control group, TA-TMA group and TA-TMA+Rg1 group. The proliferation, apoptosis and related proteins expression of endothelial cells were detected.ResultsA-TMA plasma leaded to the toxicity of endothelial cells. The expression of p-AKT, p-STAT3, and HIF-1α/Plasminogen Activator Inhibitor-1 (PAI-1) was significantly increased in TA-TMA endothelial cell model. The expression of p-STAT3 and HIF-1α was significantly reduced when MK2206 was used. The expression of HIF-1α was significantly reduced when stattic was used. Rg1 reduced the toxicity of TA-TMA endothelial cells, as well as significantly reducing the expression of both HIF-1α and PAI-1. Furthermore, Rg1 also reduced the expression of AKT/STAT3/HIF-1α pathway.ConclusionThe expression of HIF-1α/PAI-1 was significantly increased in TA-TMA cellular and animal models. The AKT/STAT3/HIF-1α pathway was active in TA-TMA endothelial cells. Rg1 reduced the toxicity of TA-TMA endothelial cells, especially reducing the expression of HIF-1α and PAI-1.
SN - 1664-3224
ER -