Research on mechanism of Wenyang Huazhuo Tongluo formula inhibiting HIF-1a/Foxm1/smad3 pathway to improve pulmonary microvascular injury of systemic sclerosis
- VernacularTitle:温阳化浊通络方体外抑制HIF-1a/Foxm1/smad3信号通路改善系统性硬化病肺微血管损伤
- Author:
Bo BIAN
1
;
Qing MIAO
;
Fan-Wu WU
;
Yi-Ling FAN
;
Jin-Li KONG
;
Hua BIAN
;
Kai LI
Author Information
- Keywords: Wenyang Huazhuo Tongluo formula; en-dothelial-to-mesenchymal transition; systemic sclero-sis; hypoxia; pulmonary microvascular injury; HIF-1a/Foxm1/smad3 pathway
- From: Chinese Pharmacological Bulletin 2024;40(11):2119-2123
- CountryChina
- Language:Chinese
- Abstract: Aim To investigate the molecular mecha-nisms of the Wenyang Huazhuo Tongluo formula in in-hibiting endothelial-to-mesenchymal transition(En-doMT)of pulmonary microvascular endothelial cells and improving pulmonary microvascular injury in sys-temic sclerosis(SSc).Methods Pulmonary micro-vascular endothelial cells were cultured with serum from SSc patients to establish SSc pulmonary microvas-cular endothelial cells.A hypoxia model was estab-lished in SSc pulmonary microvascular endothelial cells using liquid paraffin sealing,and the cells were treated with the Wenyang Huazhuo Tongluo formula or HIF-1a inhibitor KC7F2.Western blot was used to detect the protein expression levels of VE-cadherin,CD31,vimen-tin,HIF-1α,Foxm1,smad3,Tie-1,and vWF.ELISA was used to measure the concentrations of E-selectin and ICAM-1 in cell culture medium.The luciferase re-porter gene system was used to detect the promoter ac-tivity of the Foxm1 gene.Results Compared to the control group,the levels of VE-cadherin,CD31,HIF-1α,Foxm1,smad3,Tie-1,and vWF significantly de-creased under hypoxic condition,while the levels of vi-mentin,E-selectin,and ICAM-1 significantly in-creased.In addition,the cell morphology exhibited a distinct"spindle-like"myoblast morphology.Treat-ment with the Wenyang Huazhuo Tongluo formula or KC7F2 reversed these changes in protein expression levels and cell morphology induced by hypoxia.Con-clusion The Wenyang Huazhuo Tongluo formula im-proves pulmonary microvascular injury in SSc by inhib-iting the HIF-1a/Foxm1/smad3 pathway-mediated En-doMT of pulmonary microvascular endothelial cells.
