肝细胞生长因子与转化生长因子-β(1)对心房成纤维细胞纤维化的影响

[Effect of hepatocyte growth factor and transforming growth factor-β(1) on atrial fibroblasts fibrosis].

作者信息

Zhang Jian-cheng, Chen Jian-quan, Xu Chun-xuan, Chen Lin, Lin Ya-zhou, Wu Guo-sheng

机构信息

Fujian Provincial Hospital, Fuzhou, China.

出版信息

Zhonghua Xin Xue Guan Bing Za Zhi. 2012 Oct;40(10):834-9.

DOI:

PMID:23302670

Abstract

OBJECTIVE

To investigate the effect of hepatocyte growth factor (HGF) and transforming growth factor-β(1) (TGFβ(1)) on the expression of α-smooth muscle actin (α-SMA) and collagen I in human atrial fibroblast in vitro, and to explore the possible molecular mechanism of atrial fibrosis in patients with atrial fibrillation (AF).

METHODS

Human atrial fibroblast, isolated from aseptic right atrial appendage tissues of 10 sinus rhythm (SR) and 10 chronic atrial fibrillation (CAF) patients, were cultured with HGF and TGFβ(1). mRNA expressions of collagen I and α-SMA were detected by semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR), the protein expression of α-SMA was determined by immunofluorescence and Western blot.

RESULTS

(1) Compared with SR group, left atrium was significantly dilated in CAF group (t = 2.692, P < 0.05), the mRNA expression of collagen I and α-SMA of atrial fibroblasts were significantly upregulated (all P < 0.01), mRNA expression of collagen I was positively correlated with left atrial dimension (LAD) (r = 0.836, P = 0.014), AF duration (r = 0.739, P = 0.045) and α-SMA mRNA level (r = 0.886, P = 0.012). (2) Compared with SR group, the expression of α-SMA protein in CAF atrial fibroblasts were significantly increased (P < 0.01). (3) TGFβ(1) further stimulated while HGF significantly attenuated the expression of collagen I and α-SMA in CAF atrial fibroblasts (all P < 0.01).

CONCLUSIONS

Increasing expression of collagen I and α-SMA in human atrial fibroblasts might promote atria remodeling leading to the development and sustaining of AF. HGF is involved in the negative regulation on the expression of α-SMA and collagen I.

摘要

目的

研究肝细胞生长因子（HGF）和转化生长因子-β1（TGFβ1）对体外培养的人心房成纤维细胞α-平滑肌肌动蛋白（α-SMA）和Ⅰ型胶原蛋白表达的影响，探讨心房颤动（AF）患者心房纤维化的可能分子机制。

方法

从10例窦性心律（SR）和10例慢性心房颤动（CAF）患者的无菌右心耳组织中分离出人心房成纤维细胞，分别用HGF和TGFβ1进行培养。采用半定量逆转录-聚合酶链反应（RT-PCR）检测Ⅰ型胶原蛋白和α-SMA的mRNA表达，通过免疫荧光和蛋白质印迹法检测α-SMA的蛋白表达。

结果

（1）与SR组相比，CAF组左心房明显扩大（t = 2.692，P < 0.05），心房成纤维细胞中Ⅰ型胶原蛋白和α-SMA的mRNA表达明显上调（均P < 0.01），Ⅰ型胶原蛋白的mRNA表达与左心房内径（LAD）（r = 0.836，P = 0.014）、房颤持续时间（r = 0.739，P = 0.045）及α-SMA mRNA水平（r = 0.886，P = 0.012）呈正相关。（2）与SR组相比，CAF心房成纤维细胞中α-SMA蛋白表达明显增加（P < 0.01）。（3）TGFβ1进一步刺激而HGF显著减弱CAF心房成纤维细胞中Ⅰ型胶原蛋白和α-SMA的表达（均P < 0.01）。