Ginsenoside Rg1 reduces endothelial cell injury in transplant-associated thromboticmicroangiopathy by regulating the expression of HIF-1α

Purpose Transplant-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. Method We 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. Results A-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. Conclusion The 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.