The Apelin-APJ axis alleviates LPS-induced pulmonary fibrosis and endothelial mesenchymal transformation in mice by promoting Angiotensin-Converting Enzyme 2.

doi:10.1016/j.cellsig.2022.110418

科研成果详情

题名	The Apelin-APJ axis alleviates LPS-induced pulmonary fibrosis and endothelial mesenchymal transformation in mice by promoting Angiotensin-Converting Enzyme 2.
作者	Wang, Hui; Cong, Linjing; Yin, Xianghong; Zhang, Nan; Zhu, Min; Sun, Tingting; Fan, Junming; Xue, Feng; Fan, Xiaofang; Gong, Yongsheng
发表日期	2022-10
发表期刊	Cellular signalling 影响因子和分区
语种	英语
原始文献类型	Article
关键词	ACE2 Apelin-APJ axis Endothelial mesenchymal transition LPS Pulmonary fibrosis
其他关键词	LUNG ; INHIBITION ; RECEPTOR ; INJURY ; ACE2
摘要	Fibrotic alterations resulting from abnormal tissue repair after lung injury are responsible for the high mortality observed after acute respiratory distress syndrome. Therefore, the prevention and treatment of pulmonary fibrosis has been widely concerned. The Apelin-APJ axis plays an important role in the prevention and treatment of respiratory diseases and organ fibrosis. However, its underlying mechanism remains to be further studied. The aim of this study was to investigate whether the anti-pulmonary fibrosis effect of apelin-APJ axis is related to the activation of angiotensin-converting Enzyme 2 (ACE2). Here, we found that exogenous activation of the Apelin-APJ axis alleviates lipopolysaccharide (LPS)-induced pulmonary fibrosis in mice. In vitro studies revealed that Apelin-13 inhibited LPS-induced endothelial mesenchymal transition in lung microvascular endothelial cells, whereas [Ala13]-Apelin-13 (Apelin-APJ axis inhibitor) accelerated LPS-induced endothelial interstitial transformation in lung microvascular endothelial cells. Notably, angiotensin-converting enzyme 2 (ACE2) inhibitor blocks the beneficial effect of the Apelin-APJ axis activation on LPS-induced pulmonary fibrosis. This finding suggests that the Apelin-APJ axis inhibits pulmonary fibrosis by activating ACE2. Simultaneously, accumulating evidence suggests that ubiquitination may contribute to pulmonary fibrosis. Our study found that LPS increased the ubiquitination of ACE2 protein, whereas Apelin-13 inhibited it. In conclusion, exogenous activation of the Apelin-APJ axis improves LPS-induced pulmonary fibrosis in mice and may be a viable therapeutic target for pulmonary fibrosis.
资助项目	National Natural Science Foundation of China[81370171];Zhejiang Provincial Natural Science Foundation of China[LY18H010007];
出版者	ELSEVIER SCIENCE INC
ISSN	0898-6568
EISSN	1873-3913
卷号	98 页码:110418
DOI	10.1016/j.cellsig.2022.110418
页数	12
WOS类目	Cell Biology
WOS研究方向	Cell Biology
WOS记录号	WOS:000884572600001
收录类别	PUBMED ; SCIE ; SCOPUS
URL	查看原文
PubMed ID	35882286
SCOPUSEID	2-s2.0-85135104720
通讯作者地址	[Fan, Xiaofang]Institute of Hypoxia Medicine,School of Basic Medical Sciences,Wenzhou Medical University,Zhejiang,Wenzhou,325035,China
Scopus学科分类	Cell Biology
引用统计	被引频次[WOS]：0 [WOS记录] [WOS相关记录]
文献类型	期刊论文
条目标识符	https://kms.wmu.edu.cn/handle/3ETUA0LF/155381
专题	基础医学院（机能实验教学中心）
通讯作者	Fan, Xiaofang
作者单位	Institute of Hypoxia Medicine,School of Basic Medical Sciences,Wenzhou Medical University,Wenzhou,China
第一作者单位	基础医学院（机能实验教学中心）
通讯作者单位	基础医学院（机能实验教学中心）
第一作者的第一单位	基础医学院（机能实验教学中心）
推荐引用方式 GB/T 7714	Wang, Hui,Cong, Linjing,Yin, Xianghong,et al. The Apelin-APJ axis alleviates LPS-induced pulmonary fibrosis and endothelial mesenchymal transformation in mice by promoting Angiotensin-Converting Enzyme 2.[J]. Cellular signalling,2022,98:110418.
APA	Wang, Hui., Cong, Linjing., Yin, Xianghong., Zhang, Nan., Zhu, Min., ... & Gong, Yongsheng. (2022). The Apelin-APJ axis alleviates LPS-induced pulmonary fibrosis and endothelial mesenchymal transformation in mice by promoting Angiotensin-Converting Enzyme 2.. Cellular signalling, 98, 110418.
MLA	Wang, Hui,et al."The Apelin-APJ axis alleviates LPS-induced pulmonary fibrosis and endothelial mesenchymal transformation in mice by promoting Angiotensin-Converting Enzyme 2.".Cellular signalling 98(2022):110418.