Small interfering RNA against ERK1/2 attenuates cigarette smoke‑induced pulmonary vascular remodeling

Yu,Muqing; Liu,Xiansheng; Wu,Hongxu; Ni,Wang; Chen,Shixin; Xu,Yongjian

doi:10.3892/etm.2017.5160

Small interfering RNA against ERK1/2 attenuates cigarette smoke‑induced pulmonary vascular remodeling

Authors:
- Muqing Yu
- Xiansheng Liu
- Hongxu Wu
- Wang Ni
- Shixin Chen
- Yongjian Xu
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Affiliations: Department of Respiratory and Critical Care Medicine, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, P.R. China
Published online on: September 21, 2017 https://doi.org/10.3892/etm.2017.5160
Pages: 4671-4680
Copyright: © Yu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Cigarette smoke may contribute to pulmonary vascular remodeling (PVR), a result of the proliferation of pulmonary artery smooth muscle cells (PASMCs), before pulmonary hypertension in chronic obstructive pulmonary disease (COPD). Activated extracellular signal‑regulated kinases 1 and 2 (ERK1/2) are considered to be involved the process of PVR. This study investigated the potential role of ERK1/2 in the proliferation of rat PASMCs (rPASMCs) and cigarette smoke‑induced PVR in rats. A small interfering RNA (siRNA) against ERK1/2 (ERK1/2‑siRNA) was synthesized, and it significantly reduced the expression of ERK1/2 and cyclin E1, significantly increased the proportion of cells arrested at G0/G1 phase and significantly suppressed the proliferation of rPASMCs treated with cigarette smoke extract compared with controls (all P<0.05). In rats, ERK1/2‑siRNA, which was administered intranasally, also inhibited the activation of ERK1/2 and the upregulation of cyclin E1, both of which were induced after the rats were exposed to cigarette smoke for 3 months. ERK1/2‑siRNA also significantly reduced PVR (observed by vessel wall thickness and the proportion of fully muscularized vessels) in cigarette smoke‑exposed rats compared with a negative control siRNA (P<0.05). Collectively, these data indicated that ERK1/2‑siRNA could attenuate PVR in cigarette smoke‑exposed rats, and it may have therapeutic value in the treatment of COPD.

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