ERK1/2 Promotes cigarette smoke-induced rat pulmonary artery smooth muscle cells proliferation and pulmonary vascular remodeling via up-regulating cycline1 expression
ERK1/2 Promotes cigarette smoke-induced rat pulmonary artery smooth muscle cells proliferation and pulmonary vascular remodeling via up-regulating cycline1 expression
复制标题
ERK1/2通过上调CyclinE1表达促进香烟烟雾诱导的大鼠肺动脉平滑肌细胞增殖和肺血管重塑
DOI：
10.1007/s11596-013-1117-8
复制
发表时间：
2013-06-01
影响因子：
--
通讯作者：
Xu, Yong-jian
中科院分区：
文献类型：
--
作者：
Yu, Mu-qing;Liu, Xian-sheng;Xu, Yong-jian
本研究探讨ERK 1/2-cyclinE 1信号通路在香烟烟雾诱导的大鼠肺动脉平滑肌细胞（rPASMCs）增殖和肺血管重构中的作用。将24只雄性Wistar大鼠随机分为4组：对照组（C组）、S-1 M组、S-3 M组和S-6 M组（分别暴露于烟雾1、3和6个月）。HE染色和抗α-平滑肌肌动蛋白抗体染色观察肺血管重构程度。免疫组化和Western blotting检测肺血管ERK 1/2和cyclinE 1的表达。原代培养的大鼠肺动脉平滑肌细胞（rPASMCs）暴露于香烟烟雾提取物（CSE）。用ERK抑制剂PD 98059和cyclinE 1 siRNA检测ERK 1/2和cyclinE 1在CSE诱导rPASMCs增殖中的作用。通过细胞计数和5-溴-2-脱氧尿苷（BrdU）掺入来评估细胞增殖。结果表明，吸烟大鼠存在肺血管重构异常。与C组相比，烟雾暴露组ERK 1/2和cyclinE 1的表达明显增加。ERK 1/2和cyclinE 1的表达与肺血管重构程度呈正相关。PD 98059和cyclinE 1 siRNA抑制rPASMCs的增殖。PD 98059可下调cyclinE 1的表达。结果提示，ERK 1/2和cyclinE 1的表达增加可能参与了香烟烟雾诱导的大鼠肺动脉平滑肌细胞增殖异常和肺血管重构的发病机制。
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-alpha-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.