Activating Mas receptor protects human pulmonary microvascular endothelial cells against LPS-induced apoptosis via the NF-kB p65/P53 feedback pathways

作者：Huang, Weifeng; Cao, Yongmei; Liu, Yujing; Ping, Feng; Shang, Jiawei; Zhang, Zhongwei; Li, Yingchuan^*

来源：Journal of Cellular Physiology, 2019, 234(8): 12865-12875.

DOI：10.1002/jcp.27951

• apoptosis
• Mas receptor
• nuclear factor (NF)-kB p65
• P53 pathway
• pulmonary microvascular endothelial cells

The balance between Ang II/AT1R and Ang-(1-7)/Mas plays a pivotal role in the development of lipopolysaccharides (LPS)-induced acute respiratory distress syndrome. However, the mechanisms underlying the balancing process still remain unclear. Here we investigated the roles of nuclear factor (NF)-B and p53 in regulating AT1R and Mas expression. The results demonstrated that Ang II pretreatment resulted in downregulation of Mas and upregulation of AT1R, phosphorylated p65, and apoptosis in LPS-treated Human pulmonary microvascular endothelial cells (HPMVECs), but had no effect on p53 expression. Lentiviral vector-mediated P65 knockdown, but not a P53 knockdown, reversed all these effects of Ang II. On the other hand, Ang-(1-7) pretreatment lead to an increased in Mas expression and a decrease in AT1R, p53, and phosphorylated p65 expressions with suppressed apoptosis in LPS-treated cells. P65 knockdown promoted the protein expression of both AT1R and Mas while inhibiting p53 expression. P53 knockdown, but not a p65 knockdown, reversed all these effects of Ang-(1-7). Interestingly, p65 overexpression upregulated p53 and AT1R but downregulated Mas. P53 knockdown activated p65. These results suggest that there is a two-way feedback regulation between AT1R and Mas receptor via the NF-kB p65/P53 pathway, which may play a key role in LPS-induced HPMVECs apoptosis.

• 出版日期2019-8
• 单位上海交通大学