Immunohistochemical characterization of myofibroblasts appearing in isoproterenol-induced rat myocardial fibrosis
Immunohistochemical characterization of myofibroblasts appearing in isoproterenol-induced rat myocardial fibrosis
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DOI：
10.1292/jvms.18-0599
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发表时间：
2019-01-01
影响因子：
1.2
通讯作者：
Yamate, Jyoji
中科院分区：
文献类型：
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作者：
Koga, Masaaki;Kuramochi, Mizuki;Yamate, Jyoji
纤维化病变是由能够产生胶原的肌成纤维细胞形成的。肌成纤维细胞的特点是不同程度地免疫表达vimentin、desmin和α -平滑肌肌动蛋白（α - sma）。心肌纤维化的细胞特征仍在研究中。我们分析了注射异丙肾上腺素（10 mg/kg体重）后28天大鼠心肌纤维化中出现的肌成纤维细胞的免疫表型；第8小时、第1、3天病变表现为间质水肿和炎性细胞反应，第1、3、7、14、21天胶原逐渐沉积，纤维化发生，第14天病变程度最大；病变逐渐缩小，至第28天出现散发性瘢痕。表达波形蛋白和α - sma的肌成纤维细胞在第3天达到峰值，随后逐渐下降。有趣的是，在受影响的区域出现了表达Thy-1的细胞，显然对应的级别与vimentin和α - sma阳性细胞相似。他们-1在未成熟的间充质细胞中表达，如具有多能性的周细胞。一些周围细胞对未成熟间充质细胞标记物a3抗原具有免疫反应性。没有细胞与巢蛋白或胶质纤维酸性蛋白抗体反应，尽管有报道称肝肌成纤维细胞与这些抗体反应。总的来说，出现在大鼠心肌纤维化中的肌成纤维细胞可能来源于未成熟的间充质细胞，其Thy-1或a3抗原呈阳性，随后在分化过程中表达vimentin和α - sma。
Fibrotic lesion is formed by myofibroblasts capable of producing collagens. The myofibroblasts are characterized by immunoexpressions of vimentin, desmin and alpha-smooth muscle actin (alpha-SMA) in varying degrees. The cellular characteristics remain investigated in myocardial fibrosis. We analyzed immunophenotypes of myofibroblasts appearing in isoproterenol-induced myocardial fibrosis in rats until 28 days after injection (10 mg/kg body weight); the lesions developed as interstitial edema and inflammatory cell reaction on 8 hr and days 1 and 3, and fibrosis occurred on days 1, 3, 7, 14, and 21 by gradual deposition of collagens, showing the greatest grade on day 14; the lesions gradually reduced with sporadic scar until day 28. Myofibroblasts expressing vimentin and alpha-SMA increased with a peak on day 3, and then, gradually decreased onwards. Interestingly, Thy-1 expressing cells appeared in the affected areas, apparently being corresponding to the grade similar to vimentin-and alpha-SMA-positive cells. Thy-1 is expressed in immature mesenchymal cells such as pericytes with pluripotent nature. The immunoreactivity for A3-antigen, a marker for immature mesenchymal cells, was seen in some surrounding cells. There were no cells reacting with antibodies to nestin or glial fibrillary acidic protein, although hepatic myofibroblats have been reported to react with these antibodies. Collectively, myofibroblasts appearing in rat myocardial fibrosis may have been derived from immature mesenchymal cells positive for Thy-1 or A3-antigen, with thereafter showing expressions of vimentin and alpha-SMA in differentiation.