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ERK1/2 Promotes cigarette smoke-induced rat pulmonary artery smooth muscle cells proliferation and pulmonary vascular remodeling via up-regulating cycline1 expression

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Summary

This study investigated the potential role of ERK1/2-cyclinE1 signaling pathway in rat pulmonary artery smooth muscle cells (rPASMCs) proliferation and pulmonary vascular remodeling induced by cigarette smoke exposure. A total of 24 male Wistar rats were randomly divided into 4 groups: control group (C group), S-1M, S-3M and S-6M groups (animals in the groups were exposed to smoke for 1, 3, and 6 months, respectively). HE staining and anti-α-smooth muscle actin antibody staining were performed to observe the degree of pulmonary vascular remodeling. Immunohistochemistry and Western blotting were performed to evaluate ERK1/2 and cyclinE1 expression in pulmonary vessels. Primary cultured rat pulmonary artery smooth muscle cells (rPASMCs) were exposed to cigarette smoke extract (CSE). ERK inhibitor (PD98059) and cyclinE1 siRNA were used to verify the role of ERK1/2 and cyclinE1 in CSE-induced rPASMCs proliferation. Cell proliferation was assessed by cell counting and 5-bromo-2-deoxyuridine (BrdU) incorporation. Our results showed that abnormal pulmonary vascular remodeling was found in cigarette smoked rats. Compared to C group, activated ERK1/2 and cyclinE1 expression was significantly increased in smoke-exposure groups. This up-regulated expression was positively correlated with the severity of pulmonary vascular remodeling, and there was positive correlation between the expression of ERK1/2 and cyclinE1. PD98059 and cyclinE1 siRNA inhibited the proliferation of rPASMCs. The expression of cyclinE1 could be down-regulated by PD98059. Our data demonstrated that increased expression of ERK1/2 and cyclinE1 might be involved in the pathogenesis of abnormal rPASMCs proliferation and rat pulmonary vascular remodelling induced by cigarette smoke exposure.

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Authors and Affiliations

  1. Department of Respiratory Medicine, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China

    Mu-qing Yu  (余慕清), Xian-sheng Liu  (刘先胜), Hong-xu Wu  (吴宏勖), Min Xiang  (向 敏) & Yong-jian Xu  (徐永健)

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  1. Mu-qing Yu  (余慕清)
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  2. Xian-sheng Liu  (刘先胜)
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  3. Hong-xu Wu  (吴宏勖)
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  4. Min Xiang  (向 敏)
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  5. Yong-jian Xu  (徐永健)
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Corresponding author

Correspondence to Yong-jian Xu  (徐永健).

Additional information

This project was supported by the National Natural Science Foundation of China (No. 81070044).

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Yu, Mq., Liu, Xs., Wu, Hx. et al. ERK1/2 Promotes cigarette smoke-induced rat pulmonary artery smooth muscle cells proliferation and pulmonary vascular remodeling via up-regulating cycline1 expression. J. Huazhong Univ. Sci. Technol. [Med. Sci.] 33, 315–322 (2013). https://doi.org/10.1007/s11596-013-1117-8

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  • DOI: https://doi.org/10.1007/s11596-013-1117-8

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