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Notch3表达下调在诱导心肌成纤维细胞向肌成纤维细胞转化中的作用

《心脏杂志》[ISSN:1009-7236/CN:61-1268/R]

期数:
2014年第4期
页码:
384-387,402
栏目:
基础研究
出版日期:
2014-04-25

文章信息/Info

Title:
Role of Notch3 downregulation in transformation of cardiac fibroblasts to myofibroblasts
作者:
邹 倩; 张东伟; 杜朝升; 何 薇; 李聪叶; 范延红; 王海昌
(第四军医大学西京医院心血管内科，陕西 西安 710032)
Author(s):
ZOU Qian;  ZHANG Dong-wei;  DU Chao-sheng;  HE Wei;  LI Cong-ye;  FAN Yan-hong;  WANG Hai-chang
(Department of Cardiology, Xijing Hospital, Fourth Military Medical University, Xi’an 710032, Shaanxi, China)
关键词:
Notch3; 心肌成纤维细胞; 肌成细胞; 转化
Keywords:
Notch3;  Downregulation;  cardiac fibroblasts;  myofibroblasts;  transformation
分类号:
R542.2
DOI:
-
文献标识码:
A
摘要:
目的:探讨Notch3在心肌成纤维细胞（CFs）向肌成纤维细胞（MFs）转化中的作用。方法： 用胶原酶消化法分离培养SD仔鼠的CFs，将其于不同浓度的转化生长因子-β1（TGF-β1）孵育24 h。用Western blot检测CFs中平滑肌肌动蛋白α（α-SMA）及Notch3的表达量，用ELISA法检测细胞上清羟脯氨酸含量，用Real-Time PCR检测Notch3 mRNA表达量；利用RNAi法干扰CFs中Notch3的表达，用实时PCR及Western blot检测干扰效果；Western blot检测α-SMA蛋白表达量，ELISA检测各组细胞上清羟脯氨酸含量。结果： TGF-β1 可浓度依赖性地诱导CFs细胞上清羟脯氨酸含量增加和α-SMA表达增加，同时使Notch3表达下降，其中2 ng/ml，5 ng/ml，10 ng/ml 3个浓度组与对照组相比有统计学差异（P<0.05）。RNAi法干扰Notch3后，干扰组与对照组相比，Notch3 mRNA及蛋白表达均下降（P<0.05），同时，干扰组细胞上清羟脯氨酸含量及α-SMA表达均增加（P<0.05）。结论： Notch3表达下调能诱导CFs向MFs转化。
Abstract:
AIM:To investigate the role of Notch3 in the transformation of cardiac fibroblasts (CFs) to myofibroblasts (MFs). METHODS: CFs were isolated by collagenase digestion method and incubated for 24 h with different concentrations of TGF-β1. Western blot analysis was used to measure α-smooth muscle actin (α-SMA) and Notch3 expression. ELISA was used to measure hydroxyproline content in the supernatants and real-time PCR was used to measure Notch3 mRNA expression. RNAi method was employed to interfere with the expression of Notch3, and Western blot and real-time PCR analysis were employed to analyze the interference effects. RESULTS: TGF-β1 induced increases of hydroxyproline content in the supernatants and α-SMA expression dose dependently in CFs and induced decreases of Notch3 expression. Compared with those in control group, significant differences were observed in the changes at the concentrations of 2, 5, and 10 ng/ml (all P<0.05). Notch3 mRNA and protein expression decreased, and hydroxyproline content in the supernatants and α-SMA expression increased in interference group (all P<0.05). CONCLUSION: Notch3 expression downregulation can induce the transformation of CFs to MFs.

参考文献/References

[1]Brown RD,Ambler SK,Mitchell MD,et al.The cardiac fibroblast: therapeutic target in myocardial remodeling and failure[J].Annu Rev Pharmacol Toxicol,2005,4(5):657-687.
[2]Shahbaz AU,Sun Y,Bhattacharya SK,et al.Fibrosis in hypertensive heart disease: Molecular pathways and cardioprotective strategies[J].J Hyperten,2010,28(Suppl 1):S25-S32.
[3]Fan D,Takawale A,Lee J,et al.Cardiac fibroblasts,fibrosis and extracellular matrix remodeling in heart disease[J].Fibrogenesis Tissue Repair,2012,5(1):15.
[4]Quillard T,Devallière J,Coupel S,et al. Inflammation dysregulates Notch signaling in endothelial cells:Implication of Notch2 and Notch4 to endothelial dysfunction[J].Biochemical Pharmacolog,2010,80(12):2032-2041.
[5]Liu T,Hu B,Choi YY,et al.Notch1 signaling in FIZZ1 induction of myofibroblast differentiation[J].Am J Pathol,2009,174(5):1745-1755.
[6]Bielesz B, Sirin Y,Si H,et al.Epithelial Notch signaling regulates interstitial fibrosis development in the kidneys of mice and humans[J].J Clin Invest,2010,120(11):4040-4054.
[7]Chen YX,Weng ZH,Zhang SL.Notch3 regulates the activation of hepatic stellate cells[J].World J Gastroenterol,2012,18(12):1397-1403.
[8]Kennard S,Liu H,Lilly B.Transforming growth factor-beta(TGF-β1)down-regulates Notch3 in fibroblasts to promote smooth muscle gene expression[J].J Biol Chem,2008,283(3):1324-1333.
[9]Dobaczewski M,Chen W,Frangogiannis NG.Transforming Growth Factor (TGF)-β signaling in cardiac remodeling[J].J Mol Cell Cardiol,2011,51(4):600-606.
[10]MacKenna D,Summerour SR,Villarreal FJ.Role of mechanical factors in modulating cardiac fibroblast function and extracellular matrix synthesis[J].Cardiovascular Research,2000,46(2):257-263.
[11]Baum J,Duffy HS.Fibroblasts and myofibroblasts:what are we talking about?[J].J Cardiovasc Pharmacol,2011,57(4):376-379.
[12]Tomasek JJ,Gabbiani G,Hinz B,et al.Myofibroblasts and mechano-regulation of connective tissue remodelling[J].Nat Rev Mol Cell Biol,2002,3(5):349-363.
[13]Su Y,Büchler P,Gazdhar A,et al.Pancreatic regeneration in chronic pancreatitis requires activation of the notch signaling pathway[J].J Gastrointest Surg,2006, 10(9):1230-1241.

备注/Memo

备注/Memo:
收稿日期：2013-12-09.基金项目：国家自然科学基金项目资助（81370194）通讯作者：王海昌，教授，主要从事冠心病研究 Email:wanghc@fmmu.edu.cn 共同通讯作者：范延红，副教授，主要从事冠心病研究 Email:fanyh1@fmmu.edu.cn 作者简介：邹倩，硕士生 Email:21708889@qq.com
更新日期/Last Update: 2014-05-06