Activation of cardiac fibroblasts by ethanol is blocked by TGF-β inhibition.
Activation of cardiac fibroblasts by ethanol is blocked by TGF-β inhibition.
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DOI：
10.1111/acer.12111
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发表时间：
2013-08
期刊：
影响因子：
--
通讯作者：
Carver WE
中科院分区：
文献类型：
--
作者：
Law BA;Carver WE
酒精滥用是扩张型心肌病的第二大原因，这种疾病专门被称为酒精性心肌病(ACM)。啮齿动物和人类的研究表明，心肌纤维化是急性心肌梗死的结果，本实验室先前的研究表明，这种情况与转化生长因子-β(转化生长因子-β)和激活的成纤维细胞(肌成纤维细胞)的升高有关。到目前为止，还没有其他研究调查酒精对心脏成纤维细胞的直接影响。原代培养的大鼠心脏成纤维细胞在乙醇中培养，通过胶原凝胶收缩、α-平滑肌肌动蛋白(α-SMA)的表达、迁移、增殖、凋亡、I、III型胶原和转化生长因子-β的表达来检测成纤维细胞的活性。用转化生长因子-β受体1型抑制物SB 431542和可溶性重组转化生长因子-βII受体(RBII)研究转化生长因子-β在心脏成纤维细胞对乙醇反应中的作用。用100 mg/dl或更高浓度的乙醇处理心脏成纤维细胞24小时后，成纤维细胞活化和纤维化形成活性，包括收缩、α-SMA表达、迁移以及I型胶原和转化生长因子-β表达增加。未观察到成纤维细胞增殖和凋亡的变化。SB 431542和RBII对转化生长因子-β的抑制作用可减弱乙醇诱导的成纤维细胞活化。乙醇通过刺激成纤维细胞释放转化生长因子-β，直接促进心脏成纤维细胞的活化。抑制转化生长因子-β的作用可减轻乙醇诱导的肝纤维化。本研究结果支持转化生长因子-β是酒精所致心脏纤维化的重要组成部分。
Alcohol abuse is the second leading cause of dilated cardiomyopathy, a disorder specifically referred to as Alcoholic Cardiomyopathy (ACM). Rodent and human studies have revealed cardiac fibrosis to be a consequence of ACM and prior studies by this lab have associated this occurrence with elevated transforming growth factor-beta (TGF-β) and activated fibroblasts (myofibroblasts). To date there have been no other studies to investigate the direct effect of alcohol on the cardiac fibroblast. Primary rat cardiac fibroblasts were cultured in the presence of ethanol and assayed for fibroblast activation by collagen gel contraction, alpha smooth muscle- actin (α-SMA) expression, migration, proliferation, apoptosis, collagen I & III and TGF-β expression. The TGF-β receptor type 1 inhibitor compound SB 431542 and a soluble recombinant TGF-βII receptor (RbII) were used to assess the role of of TGF-β in the response of cardiac fibroblasts to ethanol. Treatment of cardiac fibroblasts with ethanol at concentrations of 100 mg/dl or higher resulted in fibroblast activation and fibrogenic activity after 24 hours including an increase in contraction, α-SMA expression, migration, and expression of collagen I and TGF-β. No changes in fibroblast proliferation or apoptosis were observed. Inhibition of TGF-β by SB 431542 and RbII attenuated the ethanol-induced fibroblast activation. Ethanol treatment directly promotes cardiac fibroblast activation by stimulating TGF-β release from fibroblasts. Inhibiting the action of TGF-β decreases the fibrogenic effect induced by ethanol treatment. The results of this study support TGF-β to be an important component in cardiac fibrosis induced by exposure to ethanol.
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DOI：
10.1073/pnas.1201840109
发表时间：
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影响因子：
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2010-09-01
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