Department of Biological Science and Technology, National Chiao Tung University, No. 75 Po-Ai Street, Hsinchu 30068, Taiwan.
Peptides. 2010 Jul;31(7):1334-40. doi: 10.1016/j.peptides.2010.03.026. Epub 2010 Mar 27.
Numerous studies have suggested that angiotensin peptides modulate the expression of angiotensin converting enzyme II (ACE2) in the cardiovascular system, but the molecular mechanisms remain poorly understood. In the present study, human cardiac fibroblasts (HCF) were used to test the regulatory effects of angiotensin II (Ang II) and angiotensin-(1-7) [Ang-(1-7)] on ACE2 expression. The results show that Ang II upregulates ACE2 expression. This action is modulated through activation of Ang II type 1 receptor (AT1R). Ang II-mediated ACE2 upregulation was blocked by antagonists of AT1R and ERK-MAPK signaling pathways. Additionally, Ang-(1-7) increased ACE2 expression, and this upregulation was inhibited by Ang-(1-7) Mas receptor blockade. Our results further reveal that the activation of p-ERK1/2 proteins plays a critical role in upregulating ACE2 in Ang-(1-7)-stimulated HCF cells. This effect occurs independently of the Ang II-AT1R signaling pathway. In conclusion, we propose that Ang II-upregulated ACE2 may increase Ang-(1-7) formation from Ang II, and that ACE2 expression is further enhanced by Ang-(1-7) in a positive feedback loop.
许多研究表明血管紧张素肽可调节心血管系统中血管紧张素转换酶 II（ACE2）的表达，但分子机制仍知之甚少。本研究以人心房成纤维细胞（HCF）为模型，检测血管紧张素 II（Ang II）和血管紧张素-(1-7) [Ang-(1-7)]对 ACE2 表达的调节作用。结果表明 Ang II 可上调 ACE2 的表达。这种作用是通过激活 Ang II 型 1 受体（AT1R）来调节的。Ang II 介导的 ACE2 上调被 AT1R 和 ERK-MAPK 信号通路拮抗剂所阻断。此外，Ang-(1-7)增加 ACE2 的表达，而 Ang-(1-7)Mas 受体阻断则抑制这种上调。我们的结果进一步表明，p-ERK1/2 蛋白的激活在 Ang-(1-7)刺激的 HCF 细胞中上调 ACE2 中起着关键作用。这种效应独立于 Ang II-AT1R 信号通路。总之，我们提出 Ang II 上调的 ACE2 可能会增加 Ang II 形成的 Ang-(1-7)，而 Ang-(1-7) 则进一步增强 ACE2 的正反馈循环表达。
