[1]武鹏宇,戴立里,唐静,等.骨形态发生蛋白-7对人肝星状细胞转化生长因子β信号转导的影响[J].陆军军医大学学报(原第三军医大学学报),2010,32(13):1433-1437.
 Wu Pengyu,Dai Lili,Tang Jing,et al.Effect of bone morphogenetic protein-7 on transforming growth factor β signaling in hepatic stellate cells[J].J Amry Med Univ (J Third Mil Med Univ),2010,32(13):1433-1437.
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骨形态发生蛋白-7对人肝星状细胞转化生长因子β信号转导的影响(/HTML )
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陆军军医大学学报(原第三军医大学学报)[ISSN:1000-5404/CN:51-1095/R]

卷:
32卷
期数:
2010年第13期
页码:
1433-1437
栏目:
论著
出版日期:
2010-07-15

文章信息/Info

Title:
Effect of bone morphogenetic protein-7 on transforming growth factor β signaling in hepatic stellate cells
作者:
武鹏宇戴立里唐静呙琳琳
重庆医科大学附属第二医院消化内科
Author(s):
Wu Pengyu Dai Lili Tang Jing Guo Linlin
Department of Gastroenterology, Second Affiliated Hospital of Chongqing Medical University, Chongqing, 400010, China
关键词:
肝硬化肝星状细胞骨形态发生蛋白质类转化生长因子
Keywords:
liver cirrhosis hepatic stellate cell bone morphogenetic protein transforming growth factors
分类号:
R322.47;R329.28;R394.2
文献标志码:
A
摘要:
目的    通过体外细胞实验,观察骨形态发生蛋白-7(bone morphogenetic protein-7,BMP-7)对转化生长因子β1(transforming growth factorβ1 ,TGFβ1)处理的人肝星状细胞(hepatic stellate cell,HSC)增殖,活化及TGFβ信号转导的影响,探索BMP7抗肝纤维化的机制。    方法    以不同浓度(80、40、20 ng/ml)BMP-7及TGFβ1(5 ng/ml)处理人肝星状细胞LX-2,CCK8法检测LX-2增殖,免疫化学染色法观察α-平滑肌动蛋白(α-SMA)与Ⅰ型胶原的表达,RT-PCR检测TGFβⅠ、Ⅱ型受体mRNA,Smad3、Smad7 mRNA的表达。    结果    经TGFβ1刺激后,LX-2增殖能力无明显改变。BMP-7(80、40、20 ng/ml)处理后,LX-2细胞增殖均被抑制,抑制率分别为28.9%、19.6%、10.5%(P<0.01)。TGFβ1处理组与细胞对照组比较,LX-2表达α-SMA 和Ⅰ型胶原增加(P<0.01),加入BMP7(20、40、80 ng/ml)处理48 h后可抑制细胞活化和胶原表达,抑制作用随处理浓度增强而增强(P<0.01, P<0.05)。5 ng/ml TGFβ1处理48 h后,TβRⅠ、TβRⅡ、Smad3 mRNA表达增加(P<0.01),Smad7 mRNA表达减少(P<0.01)。BMP-7可减少Smad3 mRNA表达(P<0.01),增加Smad7 mRNA表达(P<0.01, P<0.05),但对TβR mRNA的表达影响不显著(P>0.05)。    结论    BMP-7可抑制肝星状细胞的增殖和活化,减少Ⅰ型胶原的表达,其机制可能为抑制TGFβ/Smad通路中Smad3 mRNA表达,增加Smad7 mRNA表达,从而拮抗TGFβ1的促纤维化作用。
Abstract:
Objective    To observe the effect of bone morphogenetic protein-7 (BMP-7) on proliferation, activation and TGFβ signaling in TGFβ1 inducing hepatic stellate cells (HSC), and its anti-fibrosis mechanism.     Methods    Human HSC LX-2 cell line was treated with BMP-7 at different concentrations (80, 40, 20 ng/ml) and TGFβ1(5 ng/ml).  Proliferation of HSC LX-2 cells was detected with cell counting kit-8 (CCK8).  Expressions of α-smooth muscle actin (α-SMA) and collagen Ⅰ, as well as TGF receptors Ⅰ and Ⅱ (TGFβRⅠ, TGFβRⅡ) mRNA, Smad 3,7 mRNAs, were detected by immunocytochemical assay and RT-PCR, respectively.     Results    No significant difference was found in proliferation of LX-2 cells before and after treatment with TGFβ1. BMP-7 used at different concentrations (80, 40, 20 ng/ml) inhibited the proliferation of LX-2 with an inhibition rate of 28.9%, 19.6% and 10.5%, respectively (P<0.01). The expression level of α-SMA and collagenⅠin LX-2 was higher in TGFβ1 group than in control group (P<0.01). BMP-7 decreased the expression of α-SMA , collagenⅠ, Smad3 and Smad7 in LX-2 in a dose-dependent manner 48 h after treatment with TGFβ1 (P<0.05). The expression level of TGFβRⅠ, TGFβRⅡ and Smad3 mRNA was higher, while that of Smad7 mRNA was lower after treatment with 5 ng/ml TGFβ1 (P<0.01). BMP-7 could reduce the expression of Smad3 mRNA and increase the expression of Smad7 mRNA (P<0.05, but had no effect on the expression of TGFβR  mRNA.     Conclusion    BMP-7 inhibits the proliferation, activation and collagenⅠexpression by decreasing the Smad3 mRNA expression and increasing the Smad7 mRNA expression,thus antagonizing the role of TGFβ1 in promotion of fibrosis.

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更新日期/Last Update: 2010-07-09