Effects of hepatocyte growth factor and transforming growth factor-β1 on proli-feration of primarily cultured human atrial fibroblasts
Received:July 31, 2017  Revised:August 18, 2017
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DOI:10.11915/j.issn.1671-5403.2017.11.189
Key words:transforming growth factor-β1  hepatocyte growth factor  atrial fibrillation  atrial fibroblasts  proliferation
Author NameAffiliationE-mail
CHEN Jian-Quan Department of Cardiology, Fujian Provincial Hospital, Fuzhou 350001, China  
ZHANG Jian-Cheng Provincial Clinical School of Fujian Medical University, Fuzhou 350000, China fjzhangjiancheng@126.com 
CHEN Lin Department of Cardiology, Fujian Provincial Hospital, Fuzhou 350001, China  
LIN Ya-Zhou Department of Cardiology, Fujian Provincial Hospital, Fuzhou 350001, China  
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Abstract:
      Objective To investigate the role of hepatocyte growth factor (HGF) and transforming growth factor beta 1 (TGF-β1) on the proliferation of human atrial fibroblasts cultured in vitro, and determine the effect of HGF on the expression of TGF-β1 in human atrial fibroblasts. Methods A total of 20 patients with rheumatic heart disease (RHD) who underwent cardiac valve replacement in the Department of Cardiovascular Surgery of Fujian Provincial Hospital were recruited in this study. They were 10 cases of sinus rhythm (SR) and 10 cases of chronic atrial fibrillation (CAF), and were assigned into as SR group and CAF group accordingly. The data of left atrial diameter (LAD) were collected for each patient. After moderate right atrial appendage tissues were obtained during the operation, the atrial fibroblasts were isolated and primarily cultured. Then the obtained cells were treated with different concentrations of HGF (25,0, 100 and 200 ng/ml) and TGF-β1 (0.1,1, 10 and 100 ng/ml) for different times (12,4, 48 and 72 h), the effects of the concentrations and time periods on the proliferation of atrial fibroblasts were studied by water-soluble sulfonated tetrazolium (WST-1). The expression of TGF-β1 at mRNA level in atrial fibroblasts from the SR, CAF and HGF intervention group (the cells from CAF group after 100 ng/ml HGF treatment for 48 h) were analyzed with RT-PCR. SPSS statistics 19.0 was used for data processing. Student’s t test was used for the comparison between groups, and single factor analysis of variance was used for intergroup comparison. Results LAD was significantly larger in the CAF patients than the SR patients [(5.76±1.37) vs (4.43±0.77)cm]. HGF and TGF-β1 respectively inhibited and promoted the proliferation of human atrial fibroblasts in dose-dependent (rHGF=-0.686, rTGF-β1=0.655,P<0.05) and time-dependent manners (rHGF=0.557, rTGF-β1=0.840, P<0.05), with a peak action of 100 ng/ml HGF for 48 h, and of 10 ng/ml TGF-β1 for 48 h. TGF-β1 plus HGF showed inhibitory effect on cell proliferation. The mRNA expression level of TGF-β1 was decreased in both SR group (0.92±0.66) and HGF intervention group (0.67±0.64) when compared with CAF group (1.78±0.98, P<0.01). Conclusion The CAF patients have larger LAD and increased TGF-β1 expression. HGF inhibits TGF-β1 expression in human atrial fibroblasts, and partially counteracts the promoting role of TGF-β1 on cell proliferation.
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