Previous studies have shown that apoptosis of alveolar cells can be regulated by autocrine of angiotensin (ANG)II and its counter regulatory ACE-2/ANG1-7 axis. Our earlier study has shown that endoplasmic reticulum (ER) stress in response to seawater aspiration eventually led to apoptosis in lung tissue. In this study, we examined the hypothesis that ER stress-induced apoptosis in seawater aspiration-induced acute lung injury (ALI) might also be regulated by the ANGII/ANG1-7 system. ER stress was induced by seawater stimulation and proteasome inhibitor MG132 (an ER stress inductor). Moreover, ER stress in seawaler-stimulated lung tissues and rat pulmonary microvascular endolhelial cells (RPMVECs) promoted ANG1I expression and decreased ACE-2/ANG1-7 expression. ER stress induced by seawater stimulation also led to apoptosis. Apoptosis induced by seawater stimulation and MG132 were inhibited by ANGII receptor blocker and abrogated by the addition of ANG1-7. These results suggest that apoptosis induced by ER stress in seawater aspiration-induced ALI is regulated by ANG 1I/ANG1-7 in lung tissues and RPMVECs.
展开▼
机译：先前的研究表明，肺泡细胞的凋亡可以通过血管紧张素（ANG）II及其反调节ACE-2 / ANG1-7轴的自分泌进行调节。我们早期的研究表明，响应海水吸入的内质网（ER）应激最终导致肺组织凋亡。在这项研究中，我们检验了海水吸入诱导的急性肺损伤 （ALI） 中 ER 应激诱导的细胞凋亡也可能受 ANGII/ANG1-7 系统调节的假设。海水刺激和蛋白酶体抑制剂MG132（一种内质网应力诱导器）诱导了内质网应激。此外，海藻刺激的肺组织和大鼠肺微血管内螺旋细胞（RPMVECs）的内质网应激促进了ANG1I的表达，降低了ACE-2/ANG1-7的表达。海水刺激诱导的内质网应激也导致细胞凋亡。ANGII受体阻滞剂抑制海水刺激和MG132诱导的细胞凋亡，添加ANG1-7可消除。这些结果表明，在肺组织和RPMVECs中，ER 应激诱导的海水吸入 ALI 中细胞凋亡受 ANG 1I/ANG1-7 的调控。
展开▼
