Human and Rodent Skeletal Muscles Express Angiotensin II Type 1 Receptors
Human and Rodent Skeletal Muscles Express Angiotensin II Type 1 Receptors
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DOI：
10.3390/cells9071688
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发表时间：
2020-07-01
期刊：
影响因子：
6
通讯作者：
Powers, Scott
中科院分区：
文献类型：
--
作者：
Deminice, Rafael;Hyatt, Hayden;Powers, Scott
大量的证据表明，激活的肾素-血管紧张素系统促进骨骼肌萎缩的几个条件，包括充血性心力衰竭，慢性肾脏疾病，延长机械通气。然而，关于循环血管紧张素II（AngII）是否通过直接或间接作用促进骨骼肌萎缩存在争议;这场争论的核心是骨骼肌纤维是否表达AngII 1型受体（AT 1 Rs）的问题。虽然一些研究人员断言骨骼肌表达AT 1 R，但其他人认为骨骼肌纤维不含AT 1 R。文献中这些不一致的发现可能是研究设计缺陷的结果，需要使用严格的实验方法进行额外的研究来解决这个问题。我们测试的假设，AT 1受体在人类和大鼠骨骼肌纤维中表达。我们的前提是使用严格的，多技术的实验设计进行了测试。首先，我们建立了人类和大鼠骨骼肌纤维的血管紧张素Ⅱ配体结合试验的AT 1 Rs的位置和丰度。其次，使用一种新的和高选择性的AT 1 R抗体，我们进行了Western印迹，并确定了AT 1 R蛋白的丰度分离的单个肌纤维从人类和大鼠。最后，我们证实了AT 1 R mRNA的存在下，从大鼠分离的单肌纤维。我们的研究结果支持的假设，AT 1 Rs是存在于人类和大鼠骨骼肌纤维。此外，我们的实验提供了第一个证据表明，AT 1 R更丰富的快速，II型肌纤维相比，缓慢，I型纤维。总之，这些发现为更好地理解AngII诱导的骨骼肌萎缩的机制提供了基础。
Abundant evidence reveals that activation of the renin-angiotensin system promotes skeletal muscle atrophy in several conditions including congestive heart failure, chronic kidney disease, and prolonged mechanical ventilation. However, controversy exists about whether circulating angiotensin II (AngII) promotes skeletal muscle atrophy by direct or indirect effects; the centerpiece of this debate is the issue of whether skeletal muscle fibers express AngII type 1 receptors (AT1Rs). While some investigators assert that skeletal muscle expresses AT1Rs, others argue that skeletal muscle fibers do not contain AT1Rs. These discordant findings in the literature are likely the result of study design flaws and additional research using a rigorous experimental approach is required to resolve this issue. We tested the hypothesis that AT1Rs are expressed in both human and rat skeletal muscle fibers. Our premise was tested using a rigorous, multi-technique experimental design. First, we established both the location and abundance of AT1Rs on human and rat skeletal muscle fibers by means of an AngII ligand-binding assay. Second, using a new and highly selective AT1R antibody, we carried out Western blotting and determined the abundance of AT1R protein within isolated single muscle fibers from humans and rats. Finally, we confirmed the presence of AT1R mRNA in isolated single muscle fibers from rats. Our results support the hypothesis that AT1Rs are present in both human and rat skeletal muscle fibers. Moreover, our experiments provide the first evidence that AT1Rs are more abundant in fast, type II muscle fibers as compared with slow, type I fibers. Together, these discoveries provide the foundation for an improved understanding of the mechanism(s) responsible for AngII-induced skeletal muscle atrophy.