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

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

  • Cell Signal. 2022 Oct;98:110418. doi: 10.1016/j.cellsig.2022.110418.
Hui Wang 1 Linjing Cong 1 Xianghong Yin 1 Nan Zhang 1 Min Zhu 1 Tingting Sun 1 Junming Fan 1 Feng Xue 1 Xiaofang Fan 2 Yongsheng Gong 3
Affiliations

Affiliations

  • 1 Institute of Hypoxia Medicine, School of Basic Medical Sciences,Wenzhou Medical University, Wenzhou, China.
  • 2 Institute of Hypoxia Medicine, School of Basic Medical Sciences,Wenzhou Medical University, Wenzhou, China. Electronic address: fxbwzmc@126.com.
  • 3 Institute of Hypoxia Medicine, School of Basic Medical Sciences,Wenzhou Medical University, Wenzhou, China. Electronic address: fxbgong@126.com.
Abstract

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.

Keywords

ACE2; Apelin-APJ axis; Endothelial mesenchymal transition; LPS; Pulmonary fibrosis.

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