| 苏星宇 蒋晓敏 陈绍良.TGF-beta1 通过PI3K及ERK信号通路调节肺动脉高压过程中IGFBPs蛋白表达[J].,2016,16(8):1428-1431 |
| TGF-beta1 通过PI3K及ERK信号通路调节肺动脉高压过程中IGFBPs蛋白表达 |
| IGFBPs are Regulated by TGF-beta1 Relying on PI3K and ERK SignalingPathway in PAH |
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| DOI： |
| 中文关键词: 肺动脉高压 TGF-beta信号通路 ERK 信号通路 |
| 英文关键词: PAH TGF-betasignaling pathway ERK signaling pathway |
| 基金项目:江苏省临床科技专项基金资助（BL2013001） |
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| 中文摘要: |
| 目的：探讨大鼠肺动脉高压(PAH)过程中TGF-beta1对胰岛素样生长因子结合蛋白（IGFBP）表达调节是否依赖于PI3K及ERK
信号通路。方法：取健康成年SD 大鼠26 只，随机分成2 组：PAH组，腹腔注射1%的野百合碱，剂量为60 mg/kg；对照(C)组腹腔
注射生理盐水。于4 周后超声检测肺动脉平均压力，取肺组织做HE 染色，应用NIS-Element 系统测量中膜厚度。原代培养肺动脉
平滑肌（PASMC）细胞，分别加入TGF-beta1 及TGF-beta1 中和抗体后，Western-blot 检测IGFBP3，IGFBP5，Smad2/Smad3 表达。加入
ERK特异性抑制剂PD98059 或PI3K 抑制剂LY294002，检测IGFBP3，IGFBP5 表达。结果：野百合碱处理4 周后，肺动脉高压组
的平均肺动脉压力及右室/(左室+室间隔)比值显著高于对照组。TGF-茁1 可显著升高IGFBP3，IGFBP5 及p-Smad3 的表达（P<0.
05），而抑制TGF-beta1 则可显著降低三种蛋白的表达（P<0.05）。加入LY294002 抑制PI3K ERK 后，IGFBP3 和p-Smad2 两种蛋白的
表达量显著下调（P<0.05）。加入PD98059 抑制ERK 后可显著降低IGFBP3 及IGFBP5 的表达水平（P<0.05）。结论：PAH 中
TGF-茁1 升高可通过活化Smad2/Smad3 上调IGFBP3和IGFBP5 的表达。TGF-beta1 促进IGFBP3，IGFBP5表达的作用依赖于PI3K
及ERK 信号通路。 |
| 英文摘要: |
| Objective:To investigate the mechanism of TGF-beta1 regulating the expression of insulin-like growth factor binding
protein (IGFBP) expression in rats. To determine if the regulation of insulin-like growth factor binding protein (IGFBP) by TGF-beta1
depends on PI3K and ERK signaling pathway in rat pulmonary arterial hypertension (PAH).Methods:Twenty-six SD rats were randomly
divided into 2 groups: PAH group, intraperitoneal injection of 1% of monocrotaline. Control (C) groups were injected with saline.
Pulmonary artery pressure and HE staining were tested after four weeks. Primary pulmonary artery smooth muscle (PASMC) cells were
cultured, IGFBP3, IGFBP5, Smad2 / Smad3 were detected with or without TGF-beta1 by Western-blot. After treated with ERK inhibitor
PD98059 or PI3K inhibitor LY294002, IGFBP3, IGFBP5 were detected.Results:Four weeks after treatment, the MPAP in PAH group
were higher than control group. The PAH model leads to a significant increase in RV/ (LV+S) and pulmonary artery media thickness.
TGF-beta1 significantly increased expression of IGFBP3, IGFBP5 and p-Smad3 protein. LY294002 significantly suppressed the expression
of IGFBP3 and p-Smad2protein. What's more, PD98059 significantly suppressed the expression of IGFBP3 and IGFBP5.Conclusion:IGFBP5 and IGFBP3 can be regulated by TGF-beta1 through activating Smad2 / Smad3, which depends on PI3K and ERK signaling
pathway. |
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