Overexpression of AGT promotes bronchopulmonary dysplasis via the JAK/STAT signal pathway.

Lili Shen,Hongyan Lu,Tiancheng Zhang

doi:10.18632/oncotarget.21712

Abstract

Angiotensinogen (AGT) is involved in the production of angiotensin II which is the main mediator of action of the rennin-angiotensin system (RAS), whereas the RAS mediates the regulation of sodium homeostasis, blood pressure, and inflammation. The present study aimed to investigate the roles of the AGT in the progression of broncopulmonary dysplasia in premature newborns. By bioinformatics analysis, AGT was found to be the major node in molecular interaction networks of BPD mouse model. Quantitative PCR and western blot analyses were applied to examine AGT expression in A549 cells which were treated with the hyperoxic condition. The AGT inhibitor Valsartan and the AGT agonist ANGII were employed to investigate the roles of AGT in cell growth and the inflammation. Results show that hyperoxic treatment induced upregulation of AGT expression in A549 cells. Overexpression of AGT resulted in the inflammation via the JAK/STAT signal pathway, ultimately suppressed the proliferation of the A549 cell. In conclusion, increased expression of AGT was demonstrated to be associated with the development and progression of BPD, and may be regarded as a promising therapeutic target for BPD.

Highlights

Bronchopulmonary dysplasiais, a leading cause for many pulmonary diseases in early infancy, was histologically characterized by intense airway inflammation and lung fibrosis, even more it might lead to an increased risk for brain injury [1], severe metabolic bone disease [2]
Angiotensinogen (AGT) is involved in the production of angiotensin II which is the main mediator of action of the rennin-angiotensin system (RAS), whereas the RAS mediates the regulation of sodium homeostasis, blood pressure, and inflammation
Angiotensinogen (AGT) is involved in the production of angiotensin II which is the main mediator of action of the rennin-angiotensin system (RAS) [11] whereas the RAS mediates the regulation of sodium homeostasis, blood pressure, and inflammation [12], so it was speculated that AGT gene polymorphism might be the key biomarker predicting the risk of HSP/HSPN through its influence on the level of AGT [13]

Summary

Introduction

Bronchopulmonary dysplasiais, a leading cause for many pulmonary diseases in early infancy, was histologically characterized by intense airway inflammation and lung fibrosis, even more it might lead to an increased risk for brain injury [1], severe metabolic bone disease [2]. A considerable number of literatures on the BPD were reported to elucidate its pathogenesis and try to find an effective treatment to prevent and/or cure this disease. It was reported that treatment of hyperoxiaexposed mice with either IL1 receptor antagonist to block IL1 β or glybruide to block NIrp inflammasome resulted in decreased inflammation and increased alveolarization, it showed that the early activation of the NLRP3 inflammasome maybe a key mechanism in the development of BPD [5]. It was found that the number of transfusions was one of the key risk factors for BPD [7], other factors such as virus infection [8], nutrition [9], genetic predisposition [10] were identified to be associated with the BPD. The great progresses in elucidating the mechanism of the BPD were obtained, but completely understanding to the pathogenesis of the BPD is still in trouble due to the complexity and multifactor in aetiology

Methods

Results

Conclusion