单位：[1]Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, China-Japan Friendship Hospital, NO 2, East Yinghua Road, Chaoyang District, Beijing, 100029, China[2]Institute of Respiratory Medicine, Chinese Academy of Medical Sciences, NO 2, East Yinghua Road, Chaoyang District, Beijing, 100029, China[3]National Clinical Research Center for Respiratory Diseases, NO 2, East Yinghua Road, Chaoyang District, Beijing, 100029, China[4]Chinese Academy of Medical Sciences ＆ Peking Union Medical College, No.1 Shuaifuyuan, Wangfujing, Dongcheng District, Beijing, 100730, China[5]Department of Radiology, China-Japan Friendship Hospital, NO 2, East Yinghua Road, Chaoyang District, Beijing, 100029, China[6]Division of Cardiovascular Surgery, China-Japan Friendship Hospital, NO 2, East Yinghua Road, Chaoyang District, Beijing, 100029, China[7]Department of Respiratory and Critical Care Medicine, Beijing Anzhen Hospital, Capital Medical University, NO 2, Anzhen Road, Chaoyang District, Beijing, 100029, China首都医科大学附属安贞医院[8]Department of Lung Transplantation, the People's Hospital of Wuxi, 299 Qingyang Rd, Wuxi, 214023, China
Background: Endothelial-to-mesenchymal transition (EndMT) has been implicated in initiation and progression of pulmonary arterial hypertension (PAH). Gremlin-1 promotes vascular remodeling of PAH and mediates epithelial-mesenchymal transition, which is similar to EndMT. In the present study we investigated the potential role of gremlin-1 plays in EndMT of pulmonary artery endothelial cells (PAECs). Methods: Immunofluorescence staining was performed to detect the expression of alpha smooth muscle actin (alpha-SMA) and von Willebrand factor (VWF). Migration and angiogenic responses of PAECs were determined by transwell assay and tube formation assay, respectively. Protein expression levels were determined by western blotting. Results: Gremlin-1 induced EndMT of PAECs in a phospho-smad2/3-dependent manner. This was characterized by the loss of platelet endothelial cell adhesion molecule 1 and an increase in protein levels of a-SMA, nerve-cadherin, and matrix metalloproteinase 2. It was also determined that gremlin-1 facilitated the migration and angiogenic responses of PAECs in a dose-dependent manner. Bone morphogenetic protein 7 (BMP-7) was found to attenuate gremlin-1-mediated EndMT, migration and angiogenesis of PAECs by inducing phosphorylation of Smad1/5/8 and suppressing phosphorylation of Smad2/3. Conclusion: Gremlin-1 mediates EndMT in PAECs, and BMP-7 reverses gremlin-1-induced EndMT by an induction of p-Smad1/5/8 and suppression of p-Smad2/3.
基金：
National Key Research and Development Program of China [2016YFC0905600]; National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81570049, 81871328]; Beijing Natural Science FoundationBeijing Natural Science Foundation [7182149]
第一作者单位：[1]Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, China-Japan Friendship Hospital, NO 2, East Yinghua Road, Chaoyang District, Beijing, 100029, China[2]Institute of Respiratory Medicine, Chinese Academy of Medical Sciences, NO 2, East Yinghua Road, Chaoyang District, Beijing, 100029, China[3]National Clinical Research Center for Respiratory Diseases, NO 2, East Yinghua Road, Chaoyang District, Beijing, 100029, China
共同第一作者：
通讯作者：
通讯机构：[1]Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, China-Japan Friendship Hospital, NO 2, East Yinghua Road, Chaoyang District, Beijing, 100029, China[2]Institute of Respiratory Medicine, Chinese Academy of Medical Sciences, NO 2, East Yinghua Road, Chaoyang District, Beijing, 100029, China[3]National Clinical Research Center for Respiratory Diseases, NO 2, East Yinghua Road, Chaoyang District, Beijing, 100029, China[4]Chinese Academy of Medical Sciences ＆ Peking Union Medical College, No.1 Shuaifuyuan, Wangfujing, Dongcheng District, Beijing, 100730, China[*1]Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, China-Japan Friendship Hospital, Institute of Respiratory Medicine, Chinese Academy of Medical Sciences, National Clinical Research Center for Respiratory Diseases, NO 2, East Yinghua Road, Chaoyang District, Beijing, 100029, China[*2]Chinese Academy of Medical Sciences ＆ Peking Union Medical College, Institute of Respiratory Medicine, Chinese Academy of Medical Sciences, National Clinical Research Center for Respiratory Diseases, Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, China- Japan Friendship Hospital, NO 2, East Yinghua Road, Chaoyang District, Beijing, 100029, China
推荐引用方式(GB/T 7714)：
Zhang Yunxia,Zhang Meng,Xie Wanmu,et al.Gremlin-1 is a key regulator of endothelial-to-mesenchymal transition in human pulmonary artery endothelial cells[J].EXPERIMENTAL CELL RESEARCH.2020,390(1):doi:10.1016/j.yexcr.2020.111941.
APA：
Zhang, Yunxia,Zhang, Meng,Xie, Wanmu,Wan, Jun,Tao, Xincao...&Wang, Chen.(2020).Gremlin-1 is a key regulator of endothelial-to-mesenchymal transition in human pulmonary artery endothelial cells.EXPERIMENTAL CELL RESEARCH,390,(1)
MLA：
Zhang, Yunxia,et al."Gremlin-1 is a key regulator of endothelial-to-mesenchymal transition in human pulmonary artery endothelial cells".EXPERIMENTAL CELL RESEARCH 390..1(2020)
