Alamandine via MrgD receptor attenuates pulmonary fibrosis via NOX4 and autophagy pathway
Alamandine via MrgD receptor attenuates pulmonary fibrosis via NOX4 and autophagy pathway
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Alamandine 通过 MrgD 受体通过 NOX4 和自噬途径减轻肺纤维化
DOI：
10.1139/cjpp-2020-0662
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发表时间：
2021-09-01
影响因子：
2.1
通讯作者：
Meng, Ying
中科院分区：
文献类型：
--
作者：
Liu, Qingxia;Zheng, Bojun;Meng, Ying
阿拉曼丁（ALA）及其受体MrgD最近被鉴定为肾素-血管紧张素系统的组分，其赋予对心脏纤维化和肾纤维化的保护作用;然而，ALA对肺纤维化的作用尚不清楚。本研究旨在服务于两个目标：（i）评估ALA/MrgD轴在成纤维细胞中预防血管紧张素II（Ang II）诱导的肺纤维化的能力，和（ii）确定ALA在博来霉素（BLM）处理的C57 B/6小鼠中的作用。体内实验表明，用ALA治疗C57 B/6小鼠可预防BLM诱导的纤维化，这些发现与吡非尼酮的报告结果相似。ALA的抗肝纤维化作用是通过减轻氧化损伤和诱导自噬来实现的。此外，体外研究表明，ALA处理减弱了成纤维细胞中Ang II诱导的α-胶原I、CTGF和α-SMA的产生，这被D-Pro 7-Ang-（1-7）（一种MrgD拮抗剂）阻断。这导致氧化损伤的减轻和自噬的诱导，类似于雷帕霉素的报道。这项研究表明，ALA通过MrgD受体减轻氧化损伤和诱导自噬来减少肺纤维化。
Alamandine (ALA) and its receptor MrgD were recently identified as components of the renin-angiotensin system, which confer protection against cardio-fibrosis and renal-fibrosis; however, the effects of ALA on pulmonary fibrosis are unknown. This study was designed to serve two goals: (i) to evaluate the ALA/MrgD axis ability in the prevention of angiotensin II (Ang II) - induced pulmonary fibrosis in fibroblasts, and (ii) to determine the effect of ALA in bleomycin (BLM) - treated C57B/6 mice. In vivo experiments revealed that the treatment of C57B/6 mice with ALA prevented BLM-induced fibrosis, and these findings were similar to those reported for pirfenidone. The antifibrosis actions of ALA were mediated via alleviation of oxidative injury and autophagy induction. In addition, in vitro studies revealed that ALA treatment attenuated Ang II-induced alpha-collagen I, CTGF, and alpha-SMA production in fibroblast which was blocked by D-Pro7-Ang-(1-7), a MrgD antagonist. This led to alleviation of oxidative injury and induction of autophagy similar to that reported for rapamycin. This study demonstrated that ALA via MrgD receptor reduced pulmonary fibrosis through attenuation of oxidative injury and induction of autophagy.