Thy-1 expression, a possible marker of early myofibroblast development, in renal tubulointerstitial fibrosis induced in rats by cisplatin
Thy-1 expression, a possible marker of early myofibroblast development, in renal tubulointerstitial fibrosis induced in rats by cisplatin
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DOI：
10.1016/j.etp.2012.07.005
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发表时间：
2013-07-01
影响因子：
--
通讯作者：
Yamate, Jyoji
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文献类型：
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作者：
Yuasa, Takahiro;Juniantito, Vetnizah;Yamate, Jyoji
间质纤维化被认为是慢性肾功能衰竭的共同终末途径。肌成纤维细胞通过产生细胞外基质在肾纤维化中发挥重要作用。除了细胞骨架如波形蛋白、结蛋白和α-平滑肌肌动蛋白（α-SMA）的表达外，还研究了顺铂诱导的大鼠肾间质纤维化中Thy-1的表达，以阐明肌成纤维细胞的特征。免疫组化结果显示，肾纤维化病变中肌成纤维细胞对波形蛋白、结蛋白和α-SMA均有不同程度的反应，且表达程度随纤维化进展而增强。波形蛋白的表达是最大的，增加的表达保留，即使在瘢痕的终末期，而结蛋白和α-SMA的表达几乎完全减少瘢痕。在双重免疫荧光中，存在对波形蛋白/结蛋白、结蛋白/α-SMA或α-SMA/波形蛋白两者反应的肌成纤维细胞，表明肾肌成纤维细胞可以同时表达不同的细胞骨架。Thy-1在肾肌成纤维细胞中的表达随着纤维化的进展而增加;然而，增加的表达在瘢痕中减少，类似于结蛋白和α-SMA表达。一些表达Thy-1的肌成纤维细胞同时与波形蛋白或结蛋白反应，但没有细胞同时与Thy-1和α-SMA反应。由于分化良好的肌成纤维细胞主要以α-SMA表达为特征，并且周细胞（未成熟基质干细胞）显示对Thy-1的阳性反应，因此肾肌成纤维细胞可能是通过丢失Thy-1表达而起源于未成熟间充质细胞。这项研究首次表明，肾肌成纤维细胞可以表现出不同的间充质标志物，如波形蛋白，结蛋白，α-SMA和Thy-1;特别是，Thy-1免疫组化将用于检测肌成纤维细胞在分析化学诱导的肾脏病变的早期阶段。(C)2012 Elsevier GmbH. All rights reserved.
Interstitial fibrosis is regarded as the common final pathway in chronic renal failure. Myofibroblasts play an important role in the renal fibrosis through producing extracellular matrices. In addition to expressions of cytoskeletons such as vimentin, desmin and alpha-smooth muscle actin (alpha-SMA), Thy-1 expression was investigated in cisplatin-induced rat renal interstitial fibrosis, to clarify the characteristics of myofibroblasts. Immunohistochemically, myofibroblasts in the renal fibrotic lesions reacted to vimentin, desmin and alpha-SMA in varying degrees, and the expression degrees were increased with advancing fibrosis. Vimentin expression was the greatest and the increased expression retained even in scar at end stages, whereas desmin and alpha-SMA expressions were almost completely decreased in scar. In double immunofluorescence, there were myofibroblasts reacting to both vimentin/desmin, desmin/alpha-SMA or alpha-SMA/vimentin, indicating that renal myofibroblasts can simultaneously express different cytoskeletons. Thy-1 expression in renal myofibroblasts was increased according to progressing fibrosis; however, the increased expression was decreased in scar, similar to desmin and alpha-SMA expressions. Some myofibroblasts expressing Thy-1 reacted simultaneously to vimentin or desmin, but there were no cells reacting to both Thy-1 and alpha-SMA. Because well-differentiated myofibroblasts are characterized mainly by alpha-SMA expression and the pericytes (immature stromal stem cells) showed a positive reaction to Thy-1, renal myofibroblasts might be originated from immature mesenchymal cells through loosing Thy-1 expression. This study for the first time shows that renal myofibroblasts can variously exhibit such mesenchymal markers as vimentin, desmin, alpha-SMA and Thy-1; particularly, Thy-1 immunohistochemistry would be used to detect myofibroblasts at early stages in analyzing chemically induced renal lesions. (C) 2012 Elsevier GmbH. All rights reserved.