Alpha-smooth muscle actin (α-SMA) and nestin expression in reactive astrocytes in multiple sclerosis lesions:: potential regulatory role of transforming growth factor-beta 1 (TGF-β1)
Alpha-smooth muscle actin (α-SMA) and nestin expression in reactive astrocytes in multiple sclerosis lesions:: potential regulatory role of transforming growth factor-beta 1 (TGF-β1)
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DOI：
10.1111/j.1365-2990.2007.00910.x
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发表时间：
2008-10-01
影响因子：
5
通讯作者：
Lambrichts, I.
中科院分区：
文献类型：
--
作者：
Moreels, M.;Vandenabeele, F.;Lambrichts, I.
目的：在多种形式的中枢神经系统(CNS)损伤后，星形胶质细胞会迅速而广泛地激活。最近的研究表明，反应性星形胶质细胞的表达谱包括星形胶质细胞发育过程中存在的抗原。小胶质细胞和侵袭性巨噬细胞分泌的损伤相关细胞因子转化生长因子-β1水平升高与反应性星形胶质细胞表型和胶质瘢痕形成相关。方法：研究星形胶质细胞发育过程中表达的两种细胞骨架蛋白--α-平滑肌肌动蛋白(α-SMA)和巢蛋白在多发性硬化(MS)病变中的表达情况。此外，对原代培养的大鼠星形胶质细胞对转化生长因子-β1的反应，分析了α-SMA和Nestin的组织和表达。结果：在活动期病变和慢性活动期MS病变的高细胞边缘，α-SMA免疫染色显示反应性星形胶质细胞亚群，而大多数反应性星形胶质细胞表达Nestin。表达反应性星形胶质细胞的α-SMA和Nestin与表达转化生长因子-β1的巨噬细胞或小胶质细胞关系密切。此外，在表达α-SMA或Nestin的星形胶质细胞中也检测到了转化生长因子-β1的表达。我们的体外实验表明，转化生长因子-β1调节星形胶质细胞中α-SMA和Nestin的组织和表达。结论：活动期MS病变中反应性星形胶质细胞重新表达α-SMA和Nestin。这些结果进一步阐明了中枢神经系统损伤后星形胶质细胞活性的调节，这对星形胶质细胞对病理情况的适应具有重要意义。
Aims: Rapid and extensive activation of astrocytes occurs subsequent to many forms of central nervous system (CNS) injury. Recent studies have revealed that the expression profile of reactive astrocytes comprises antigens present during astrocyte development. Elevated levels of the injury-related cytokine transforming growth factor-beta 1 (TGF-beta 1) secreted by microglial cells and invading macrophages have been correlated with the reactive astrocyte phenotype and glial scar formation. Methods: In the present study, the expression profile of alpha-smooth muscle actin (alpha-SMA) and nestin, two cytoskeletal proteins expressed during astrocyte development, was studied in multiple sclerosis (MS) lesions. In addition, alpha-SMA and nestin organization and expression were analysed in rat primary astrocyte cultures in response to TGF-beta 1. Results: In active lesions and in the hypercellular margin of chronic active MS lesions, immunostaining for alpha-SMA revealed a subpopulation of reactive astrocytes, whereas the majority of reactive astrocytes expressed nestin. alpha-SMA and nestin expressing reactive astrocytes were in close relationship with TGF-beta 1 expressing macrophages or microglia. In addition, TGF-beta 1 expression within alpha-SMA or nestin expressing astrocytes was also detected. Our in vitro experiments showed that TGF-beta 1 regulated the organization and expression of alpha-SMA and nestin in astrocytes. Conclusions: Reactive astrocytes in active MS lesions re-express alpha-SMA and nestin. We suggest that the in vivo re-expression might be under regulation of TGF-beta 1. These results further clarify the regulation of astrocyte activity after CNS injury, which is important for the astroglial adaptation to pathological situations.