Macrophage-Derived Legumain Promotes Pulmonary Hypertension by Activating the MMP (Matrix Metalloproteinase)-2/TGF (Transforming Growth Factor)-beta 1 Signaling
文献类型：期刊论文
| 作者 | Bai, Peiyuan2; Wan, Naifu2; Lyu, Ankang2; Yu, Tingting3; Lyu, Luheng4; Zuo, Caojian5; Wan, Qiangyou5; Fu, Jie1; He, Yuhu6; Jia, Daile7 |
| 刊名 | ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
 |
| 出版日期 | 2019 |
| 卷号 | 39期号:4页码:E130-E145 |
| 关键词 | extracellular matrix hypertension hypoxia macrophages transforming growth factor |
| ISSN号 | 1079-5642 |
| DOI | 10.1161/ATVBAHA.118.312254 |
| 文献子类 | Article |
| 英文摘要 | Objective- Macrophages participate in the pathogenesis of pulmonary arterial hypertension (PAH). Lgmn (Legumain), a newly discovered cysteine proteinase belonging to the C13 peptidase family, is primarily expressed in macrophages; however, its roles in PAH remain unknown. Approach and Results- Herein, Lgmn was upregulated in lung tissues of PAH mice subjected to hypoxia plus SU5416 and PAH rats challenged with monocrotaline. Global Lgmn ablation and macrophage-specific ablation alleviated PAH compared with wild-type mice, evident from a reduction in right ventricular systolic pressure, the ratio of the right ventricular wall to the left ventricular wall plus the septum, the pulmonary vascular media thickness, and pulmonary vascular muscularization. Increased expression of ECM (extracellular matrix) proteins was correlated with MMP (matrix metalloproteinase)-2 activation and TGF (transforming growth factor)-beta 1 signaling in the PAs. Although Lgmn did not affect inflammatory cell infiltration and PA smooth muscle cell proliferation, it drove increased the synthesis of ECM proteins via MMP-2 activation. MMP-2 hydrolyzed the TGF-beta 1 precursor to the active form. An Lgmn-specific inhibitor markedly ameliorated PAH. Clinically, serum Lgmn levels were closely associated with the severity of idiopathic PAH. Conclusions- Our results indicate that Lgmn inhibition could be an effective strategy for preventing or delaying PAH. |
| 学科主题 | Hematology ; Cardiovascular System & Cardiology |
| WOS关键词 | EXTRACELLULAR-MATRIX ; MAMMALIAN LEGUMAIN ; EXPRESSION ; INHIBITION ; APOPTOSIS ; TRANSFORMING-GROWTH-FACTOR-BETA-1 ; EVOLUTIONARY ; RECRUITMENT ; SECRETION ; PATHOLOGY |
| 语种 | 英语 |
| WOS记录号 | WOS:000478872000003 |
| 出版者 | LIPPINCOTT WILLIAMS & WILKINS |
| 版本 | 出版稿 |
| 源URL | [http://202.127.25.144/handle/331004/607]  |
| 专题 | 中国科学院上海生命科学研究院营养科学研究所 |
| 作者单位 | 1.Wuhan Univ, Renmin Hosp, Dept Pediat, Wuhan, Hubei, Peoples R China; 2.Shanghai Jiao Tong Univ, Sch Med, Ruijin Hosp, Dept Cardiol, 197 Ruijiner Rd, Shanghai 200025, Peoples R China; 3.Shanghai Jiao Tong Univ, Sch Med, Xinhua Hosp, Shanghai Key Lab Childrens Environm Hlth, Shanghai, Peoples R China; 4.Univ Miami, Sch Arts & Sci, Biol Major, Coral Gables, FL 33124 USA; 5.Univ Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Nutr Sci, Shanghai, Peoples R China; 6.Cent S Univ, Xiangya Hosp 2, Dept Cardiol, Changsha, Hunan, Peoples R China; 7.Fudan Univ, Zhongshan Hosp, Dept Cardiol, Shanghai, Peoples R China, |
| 推荐引用方式 GB/T 7714 | Bai, Peiyuan,Wan, Naifu,Lyu, Ankang,et al. Macrophage-Derived Legumain Promotes Pulmonary Hypertension by Activating the MMP (Matrix Metalloproteinase)-2/TGF (Transforming Growth Factor)-beta 1 Signaling[J]. ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY,2019,39(4):E130-E145. |
| APA | Bai, Peiyuan.,Wan, Naifu.,Lyu, Ankang.,Yu, Tingting.,Lyu, Luheng.,...&,.(2019).Macrophage-Derived Legumain Promotes Pulmonary Hypertension by Activating the MMP (Matrix Metalloproteinase)-2/TGF (Transforming Growth Factor)-beta 1 Signaling.ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY,39(4),E130-E145. |
| MLA | Bai, Peiyuan,et al."Macrophage-Derived Legumain Promotes Pulmonary Hypertension by Activating the MMP (Matrix Metalloproteinase)-2/TGF (Transforming Growth Factor)-beta 1 Signaling".ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY 39.4(2019):E130-E145. |
入库方式： OAI收割
来源：上海营养与健康研究所
浏览0
下载0
收藏0
其他版本
除非特别说明，本系统中所有内容都受版权保护，并保留所有权利。