Regulation of glial development by cystatin C
Regulation of glial development by cystatin C
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DOI：
10.1111/j.1471-4159.2006.04169.x
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发表时间：
2007-01-01
影响因子：
4.7
通讯作者：
Ikenaka, Kazuhiro
中科院分区：
文献类型：
--
作者：
Hasegawa, Akiko;Naruse, Masae;Ikenaka, Kazuhiro
半胱氨酸蛋白酶抑制剂C（CysC）是一种内源性半胱氨酸蛋白酶抑制剂，由成人脑中成熟的星形胶质细胞产生。以前，我们分离出CysC作为激活胶质细胞酸性蛋白（GFAP）启动子的因子，并表明CysC在发育过程中在星形胶质细胞祖细胞中表达。在这里，我们表明，蛋白酶抑制剂的活性每天增加的条件培养基中，这种活性主要是从原代培养细胞中释放的CysC的结果。将人CysC添加到原代脑细胞的培养基中增加了GFAP阳性细胞和nestin阳性细胞的数量。人CysC也增加了胚胎脑形成的神经球的数量，因此它以类似于糖基化大鼠CysC的方式增加了神经干细胞/前体细胞的数量。另一方面，加入中和抗体大大减少了GFAP和谷氨酸天冬氨酸转运蛋白（GLAST）阳性星形胶质细胞的数量。这种下降被CysC逆转，但不是由另一种半胱氨酸蛋白酶抑制剂。因此，CysC促进星形胶质细胞发育似乎与其蛋白酶抑制剂活性无关。抗体增加了少突胶质细胞及其前体细胞的数量。因此，CysC除了对神经干细胞/前体细胞的活性外，还改变神经胶质细胞的发育。
Cystatin C (CysC) is an endogenous cysteine proteases inhibitor produced by mature astrocytes in the adult brain. Previously we isolated CysC as a factor activating the glial fibrillary acidic protein (GFAP) promoter, and showed that CysC is expressed in astrocyte progenitors during development. Here we show that protease inhibitor activity increased daily in conditioned medium, and that this activity was mainly a result of CysC released from primary cultured cells. Human CysC added to the culture medium of primary brain cells increased the number of GFAP-positive and nestin-positive cells. Human CysC also increased the number of neurospheres formed from embryonic brain, and thus it increases the number of neural stem/precursor cells in a manner similar to glycosylated rat CysC. The addition of a neutralizing antibody, on the other hand, greatly decreased the number of GFAP and glutamate aspartate transporter (GLAST)-positive astrocytes. This decrease was reversed by the addition of CysC but not by another cysteine protease inhibitor. Thus, the promotion of astrocyte development by CysC appears to be independent of its protease inhibitor activity. The antibody increased the number of oligodendrocytes and their precursors. Therefore, CysC modifies glial development in addition to its activity against neural stem/precursor cells.