Angiotensin-(1-7) attenuates disuse skeletal muscle atrophy in mice via its receptor, Mas.
Angiotensin-(1-7) attenuates disuse skeletal muscle atrophy in mice via its receptor, Mas.
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DOI：
10.1242/dmm.023390
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发表时间：
2016-04
影响因子：
4.3
通讯作者：
Cabello-Verrugio C
中科院分区：
文献类型：
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作者：
Morales MG;Abrigo J;Acuña MJ;Santos RA;Bader M;Brandan E;Simon F;Olguin H;Cabrera D;Cabello-Verrugio C
固定是一种废用形式，其特征是力量和肌肉质量的丧失。其中主要特征是IGF-1/Akt信号传导减少，泛素-蛋白酶体信号传导增加，导致肌球蛋白重链降解加剧。经典肾素-血管紧张素系统（RAS）的激活导致骨骼肌的有害影响，包括肌肉萎缩。相反，血管紧张素-(1-7)[Ang-(1-7)]，一种非经典RAS的肽，在骨骼肌中产生有益作用。然而，Ang-(1-7)在骨骼肌失用性萎缩中独立于经典RAS激活的作用尚未得到评估。因此，我们在雄性、12周龄野生型（WT）和Mas敲除型（Mas KO）小鼠的后肢单侧固定的情况下，对Ang-(1-7)和Mas受体在体内废用性肌萎缩中的功能进行了1天和14天的评估。此外，我们评估了IGF-1/IGFR-1/Akt信号通路和泛素蛋白酶体通路表达对Ang-(1-7)固定诱导的肌肉萎缩的影响。我们的研究结果发现，Ang-(1-7)可以防止肌肉力量下降，肌纤维直径减少，肌球蛋白重链水平降低，并诱导atroggin -1和MuRF-1表达，所有这些通常发生在固定期间。分析表明，Ang-(1-7)通过IGFR-1和Akt磷酸化增加IGF-1/IGFR-1/Akt通路信号，并同时激活Akt的两个下游靶点p70S6K和FoxO3。在Mas KO小鼠中未观察到Ang-(1-7)的这些抗萎缩作用，表明Mas受体的关键参与。本报道首次提出Ang-(1-7)通过Mas受体参与废用性骨骼肌萎缩，并参与IGF-1/IGFR-1/Akt/p70S6K/FoxO3机制。摘要：在本文中，作者证明了一种主要作用于心血管系统的肽可以预防因废弃引起的骨骼肌损伤。
Immobilization is a form of disuse characterized by a loss of strength and muscle mass. Among the main features are decreased IGF-1/Akt signalling and increased ubiquitin-proteasome pathway signalling, which induce greater myosin heavy chain degradation. Activation of the classical renin-angiotensin system (RAS) causes deleterious effects in skeletal muscle, including muscle wasting. In contrast, angiotensin-(1-7) [Ang-(1-7)], a peptide of the non-classical RAS, produces beneficial effects in skeletal muscle. However, the role of Ang-(1-7) in skeletal muscle disuse atrophy and independent of classical RAS activation has not been evaluated. Therefore, we assessed the functions of Ang-(1-7) and the Mas receptor in disuse muscle atrophy in vivo using unilateral cast immobilization of the hind limb in male, 12-week-old wild-type (WT) and Mas-knockout (Mas KO) mice for 1 and 14 days. Additionally, we evaluated the participation of IGF-1/IGFR-1/Akt signalling and ubiquitin-proteasome pathway expression on the effects of Ang-(1-7) immobilization-induced muscle atrophy. Our results found that Ang-(1-7) prevented decreased muscle strength and reduced myofiber diameter, myosin heavy chain levels, and the induction of atrogin-1 and MuRF-1 expressions, all of which normally occur during immobilization. Analyses indicated that Ang-(1-7) increases IGF-1/IGFR-1/Akt pathway signalling through IGFR-1 and Akt phosphorylation, and the concomitant activation of two downstream targets of Akt, p70S6K and FoxO3. These anti-atrophic effects of Ang-(1-7) were not observed in Mas KO mice, indicating crucial participation of the Mas receptor. This report is the first to propose anti-atrophic effects of Ang-(1-7) via the Mas receptor and the participation of the IGF-1/IGFR-1/Akt/p70S6K/FoxO3 mechanism in disuse skeletal muscle atrophy. Summary: In this article, the authors demonstrate that a peptide with actions mainly in the cardiovascular system prevents the skeletal muscle damage induced by disuse.