Inhibition of angiotensin II-induced contraction of human airway smooth muscle cells by angiotensin-(1-7) via downregulation of the RhoA/ROCK2 signaling pathway

Li,Ning; Cai,Ruijun; Niu,Yi; Shen,Bin; Xu,Jian; Cheng,Yuanxiong

doi:10.3892/ijmm.2012.1080

Inhibition of angiotensin II-induced contraction of human airway smooth muscle cells by angiotensin-(1-7) via downregulation of the RhoA/ROCK2 signaling pathway

Authors:
- Ning Li
- Ruijun Cai
- Yi Niu
- Bin Shen
- Jian Xu
- Yuanxiong Cheng
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Affiliations: Department of Respiratory Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, P.R. China, Department of Thoracic Cardiovascular Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, P.R. China, Department of Kidney Transplantation, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, P.R. China
Published online on: July 27, 2012 https://doi.org/10.3892/ijmm.2012.1080
Pages: 811-818

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Abstract

Sustained renin-angiotensin system (RAS) activation in asthmatic patients plays a crucial role in airway hyperresponsiveness and airflow limitation. Angiotensin II (Ang II), as a key peptide of RAS, contributes to the contraction of human airway smooth muscle by activating the RhoA/Rho-associated coiled-coil containing protein kinase 2 (ROCK2) signaling pathway. Angiotensin-(1-7) [Ang-(1-7)], is a component of the angiotensin I converting enzyme 2 (ACE2)-Ang-(1-7)-Mas axis which counteracts the detrimental effects of the ACE- Ang II-angiotensin type 1 receptor (AT1R) axis in vivo; however, whether Ang-(1-7) can inhibit the effect of Ang II in the contraction of human airway smooth muscle cells (HASMCs) is unknown. In our study, collagen gel lattices and immunofluorescence were used to evaluate the contraction of HASMCs induced by Ang II. Real-time PCR and western blot analysis were performed to confirm the regulatory mechanism and the participating signaling pathway. Ang II caused the contraction of HASMCs; this effect was reversed by Ang‑(1‑7). In addition, irbesartan and A779, which are inhibitors of AT1R and Mas, respectively, attenuated the effect of Ang II and Ang-(1-7). Furthermore, Y-27632, an inhibitor of ROCK2, attenuated the Ang II-induced contraction of HASMCs by blocking the RhoA/ROCK2 signaling pathway which is involved in this contraction, and thus may be a major regulator involved in the basal maintenance of contractility in HASMCs. These data demonstrate that Ang II induces the contraction of HASMCs and that this effect can be reversed by Ang-(1-7), partially through the downregulation of of the RhoA/ROCK2 signaling pathway.

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