Department of Cardiology, the First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, 210029, Jiangsu, China.
Department of Cardiology, Yangpu Hospital, Tongji University School of Medicine, Shanghai, China.
Cell Commun Signal. 2023 Jul 24;21(1):181. doi: 10.1186/s12964-023-01168-3.
Alamandine (Ala), a ligand of Mas-related G protein-coupled receptor, member D (MrgD), alleviates angiotensin II (AngII)-induced cardiac hypertrophy. However, the specific physiological and pathological role of MrgD is not yet elucidated. Here, we found that MrgD expression increased under various pathological conditions. Then, MrgD knockdown prevented AngII-induced cardiac hypertrophy and fibrosis via inactivating Gα-mediacted downstream signaling pathways, including the phosphorylation of p38 (p-P38), while MrgD overexpression induced pathological cardiac remodeling. Next, Ala, like silencing MrgD, exerted its cardioprotective effects by inhibiting Ang II-induced nuclear import of MrgD. MrgD interacted with p-P38 and promoted its entry into the nucleus under Ang II stimulation. Our results indicated that Ala was a blocking ligand of MrgD that inhibited downstream signaling pathway, which unveiled the promising cardioprotective effect of silencing MrgD expression on alleviating cardiac remodeling. Video Abstract.
阿拉曼丁（Ala）是 Mas 相关 G 蛋白偶联受体成员 D（MrgD）的配体，可减轻血管紧张素 II（AngII）诱导的心肌肥厚。然而，MrgD 的具体生理和病理作用尚未阐明。在这里，我们发现 MrgD 在各种病理条件下表达增加。然后，MrgD 敲低通过使 Gα介导的下游信号通路失活，包括 p38 的磷酸化（p-P38），从而防止 AngII 诱导的心肌肥厚和纤维化，而 MrgD 过表达诱导病理性心脏重塑。接下来，Ala 像沉默 MrgD 一样，通过抑制 Ang II 诱导的 MrgD 的核内易位发挥其心脏保护作用。MrgD 在 Ang II 刺激下与 p-P38 相互作用并促进其进入细胞核。我们的结果表明，Ala 是 MrgD 的阻断配体，可抑制下游信号通路，揭示了沉默 MrgD 表达对减轻心脏重塑的有希望的心脏保护作用。视频摘要。
