α8β1 integrin is upregulated in myofibroblasts of fibrotic and scarring myocardium
α8β1 integrin is upregulated in myofibroblasts of fibrotic and scarring myocardium
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DOI：
10.1016/j.yjmcc.2003.11.007
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发表时间：
2004-03-01
影响因子：
5
通讯作者：
Thibault, G
中科院分区：
文献类型：
--
作者：
Bouzeghrane, F;Mercure, C;Thibault, G
整合素介导细胞与细胞外基质 (ECM) 的附着，调节迁移、增殖和分化。我们之前报道过培养的心脏成纤维细胞中存在α8β1整合素。扩展这一信息，我们在正常大鼠心肌组织中定位了 α8β1 整合素，并研究了其在长期注射血管紧张素 II（Ang II，500 ng/kg/min）（一种公认的促纤维化因子）的大鼠中的表达模式。通过结合测定、蛋白质印迹和免疫组织化学分析α8β1-整合素表达。在正常心肌中，在成纤维细胞以及心外膜、心内膜和瓣膜中发现了 α8 的免疫组织化学染色。心脏动脉中层的血管平滑肌细胞（VSMC）也呈阳性染色。 14-d-Ang II 输注后，纤连蛋白染色以及天狼星红胶原染色显示广泛的间质和血管周围纤维化。还记录了心室平滑肌 (SM) α-肌动蛋白阳性成纤维细胞（肌成纤维细胞）中 α8 整合素表达的增加。通过结合测定和蛋白质印迹证实了α8β1整合素的上调。微观疤痕是修复性纤维化的一个特征，被基质蛋白和α8-和SM-α-肌动蛋白强阳性肌成纤维细胞侵入。结果表明，在大鼠成年心肌中，α8β1整合素在成纤维细胞和VSMC中表达。在注射 Ang II 的动物中，左心室和动脉中的 α8β1-整合素表达增强。 α8β1 整合素对成纤维细胞和 ECM 蛋白的协调调节提出了这种整合素可能参与导致纤维化的基质成分沉积的可能性。 (C) 2003 Elsevier Ltd. 保留所有权利。
Integrins mediate cell attachment to the extracellular matrix (ECM) regulating migration, proliferation, and differentiation. We previously reported the presence of alpha8beta1 integrin on cultured cardiac fibroblasts. Extending this information, we localized alpha8beta1 integrin in normal rat myocardial tissue, and investigated its expression pattern in rats chronically infused with angiotensin II (Ang II, 500 ng/kg/min), a well-recognized profibrotic factor. alpha8beta1-integrin expression was analyzed by binding assay, western blotting, and immunohistochemistry. In normal myocardium, immunohistochemical staining for alpha8 was found in fibroblasts, as well as in the epicardium, endocardium, and valves. Vascular smooth muscle cells (VSMCs) of the media of cardiac arteries also stained positively. After 14-d-Ang II infusion, staining for fibronectin, as well as collagen staining by Sirius red, revealed extensive interstitial and perivascular fibrosis. Increased expression of alpha8 integrin in ventricular smooth muscle (SM) alpha-actin-positive fibroblasts (myofibroblasts) was also recorded. The upregulation of alpha8beta1 integrin was confirmed by binding assay and by western blotting. Microscopic scars, a characteristic of reparative fibrosis, were invaded by matrix proteins and by strongly alpha8- and SM alpha-actin-positive myofibroblasts. The results indicate that, in rat adult myocardium, alpha8beta1 integrin is expressed in fibroblasts and VSMC. In Ang II-infused animals, alpha8beta1-integrin expression was enhanced in the left ventricle and arteries. The coordinate regulation of alpha8beta1 integrin on fibroblasts and ECM proteins raises the possibility that this integrin is implicated in the deposition of matrix components leading to fibrosis. (C) 2003 Elsevier Ltd. All rights reserved.