Small-molecule inhibitor LF3 restrains the development of pulmonary hypertension through the Wnt/β-catenin pathway

查看全文 作　　者：Yong [1,2]Lei;Qi [1]Yang;Yongmei [1,3]Nie;Juyi [1]Wan;Mingbin [1,3,4]Deng

机构地区：[1]Department of Cardiovascular Surgery,Affiliated Hospital of Southwest Medical University,Luzhou 646000,China;[2]Department of Cardiothoracic Surgery,Nanchong Center Hospital,The Second Clinical College,North Sichuan Medical College,Nanchong 637000,China;[3]Key Laboratory of Cardiovascular and Metabolic of Luzhou City,Luzhou 646000,China;[4]Sichuan Clinical Research Center for Birth Defects,Luzhou 646000,China

出　　处：《Acta Biochimica et Biophysica Sinica》索引2021年第53卷第10期,共13页

基　　金：This work was supported in part by the grants from the Key R&D projects of Sichuan Science and Technology Department(No.2019YFSO531);the Sichuan Province Science and Technology Projects(No.2021YFH0148);the Science and Technology Strategic Cooperation Programs of Luzhou Municipal People's Governmentand Southwest Medical University(No.2019LZXNYDJ30);the Sichuan Science and Technology Grant for Overseas Students(No.19059). 摘　　要：Pulmonary hypertension(PH)associated with congenital heart disease is a progressive hemodynamic disease that can lead to increased pulmonary vascular resistance,vascular remodeling,and even right heart failure and death.LF3 is a novel inhibitor of the reporter gene activity ofβ-catenin/TCF4 interaction in the Wnt/β-catenin signal pathway.However,whether this action of LF3 can prevent PH development remains unclear.In this study,we investigated the therapeutic effect of LF3 in rat primary pulmonary artery smooth muscle cells(PASMCs)of the PH model.We found that LF3 inhibited the decrease in pulmonary artery acceleration time and ejection time by ultra-high-resolution ultrasound imaging and blocked the increase of pulmonary artery systolic pressure by using the BL420 biological function experimental system and right ventricular hypertrophy index by the electronic scales.Simultaneously,it prevented the increase ofα-smooth muscle actin and fibronectin and the decrease of elastin in pulmonary arteries of rats in the PH group,as revealed by an immunohistochemical analysis.Moreover,cell proliferation and migration assays showed that LF3 significantly reduced the proliferation and migration of PASMCs.Western blotting and quantitative real-time polymerase chain reaction analyses revealed that LF3 suppressed the expression of proliferating cell nuclear antigens and Bcl-2 and increased the expression of Bax but did not alter the expressions ofβ-catenin and TCF4.Taken together,LF3 can reduce the migration and proliferation of PASMCs and induce their apoptosis to prevent the development of PH.It would be worthwhile to explore the potential use of LF3 in the treatment of PH. 关键词：LF3 pulmonary hypertension pulmonary artery smooth muscle cell Β-CATENIN TCF4

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Small-molecule inhibitor LF3 restrains the development of pulmonary hypertension through the Wnt/β-catenin pathway

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