J Mol Neurosci. 2013 Nov;51(3):959-66. doi: 10.1007/s12031-013-0080-y.
Wild type p53-induced phosphatase 1 (Wip1) is a phosphatase which belongs to protein phosphatase type 2C family, which have been predominantly linked to cell growth and to cellular stress signaling. Numerous downstream targets of Wip1 have been identified, and genetic studies confirm that some play a part in tumorigenesis. Recent evidence highlights a new role for Wip1 in the regulation of NF-κB p65, which indicated that it might play a critical role in immune system. However, its regulation role in central nervous system (CNS) remains poorly understood. To elaborate whether Wip1 was involved in CNS injury, we performed a neuroinflammatory model by lipopolysaccharide (LPS) lateral-ventral injection in adult rats.Wip1 expression was strongly upregulated in active astrocytes in inflamed brain cortex. In vitro studies indicated that the upregulation of Wip1 may be involved in the subsequent astrocytic activation following LPS exposure, and knockdown of Wip1 in primary astrocytes by siRNA showed that Wip1 inhibited the synthesis of TNF-α. Collectively, these results suggested that Wip1 may be important in host defense in CNS immune response, which might provide a potent therapeutic target of neuroinflammation.
野生型 p53 诱导的磷酸酶 1（Wip1）是一种属于蛋白磷酸酶 2C 家族的磷酸酶，主要与细胞生长和细胞应激信号转导有关。已经鉴定出 Wip1 的许多下游靶标，遗传研究证实其中一些靶标在肿瘤发生中起作用。最近的证据强调了 Wip1 在 NF-κB p65 调节中的新作用，这表明它可能在免疫系统中发挥关键作用。然而，其在中枢神经系统（CNS）中的调节作用仍知之甚少。为了阐述 Wip1 是否参与中枢神经系统损伤，我们通过在成年大鼠侧脑室注射脂多糖（LPS）建立神经炎症模型。在炎症大脑皮层中，活性星形胶质细胞中 Wip1 的表达强烈上调。体外研究表明，LPS 暴露后 Wip1 的上调可能涉及随后的星形胶质细胞激活，并且用 siRNA 在原代星形胶质细胞中敲低 Wip1 表明 Wip1 抑制了 TNF-α 的合成。总之，这些结果表明 Wip1 在中枢神经系统免疫反应中的宿主防御中可能很重要，这可能为神经炎症提供一个有效的治疗靶点。
