Na Yeo-Jung, Jin Jae-Kwang, Kim Jae-Il, Choi Eun-Kyoung, Carp Richard I, Kim Yong-Sun
Ilsong Institute of Life Science, College of Medicine, Hallym University, Anyang, Gyeonggi-do, South Korea.
J Neurochem. 2007 Oct;103(2):637-49. doi: 10.1111/j.1471-4159.2007.04769.x.
Scrapie is characterized histologically, in part, by astrogliosis in brain and spinal cord. However, the mechanisms of astrogliosis in brain injury occurring during prion infection are not well understood. In this study, we investigated the expression levels and cellular localization of Janus kinase (JAK) -signal transducers and activators of transcription (STAT) signaling molecules and growth factors such as leukemia inhibitory factor (LIF) and ciliary neurotropic factor (CNTF) by western blot analysis and immunohistochemistry. We found that expression levels of LIF and CNTF were increased in scrapie-infected brains and phosphorylated (p)-JAK2, p-STAT1 (Ser727 and Tyr701), p-STAT3 (Tyr705), and glial fibrillary acidic protein were expressed strongly in scrapie-infected brains. Moreover, we found that p-STAT1 and p-STAT3 were found mainly in the nucleus in scrapie-infected brains. Immunohistochemically, p-STAT1 was colocalized with LIF and CNTF and p-JAK2 in many reactive astrocytes in scrapie-infected brains. In contrast, immunostaining for p-STAT3 was found in comparatively few astrocytes in limited regions; p-STAT3 staining merged with p-JAK2 in hippocampus sections of scrapie-infected brains. Taken together, our results suggest that activation of JAK2-STAT1 signaling pathway occurred in reactive astrocytes in hippocampus of scrapie-infected brains.
瘙痒病在组织学上的部分特征是脑和脊髓中的星形胶质细胞增生。然而，朊病毒感染期间脑损伤中星形胶质细胞增生的机制尚未完全明确。在本研究中，我们通过蛋白质免疫印迹分析和免疫组织化学研究了Janus激酶（JAK）-信号转导子和转录激活子（STAT）信号分子以及白血病抑制因子（LIF）和睫状神经营养因子（CNTF）等生长因子的表达水平和细胞定位。我们发现，瘙痒病感染的脑中LIF和CNTF的表达水平升高，并且磷酸化（p）-JAK2、p-STAT1（Ser727和Tyr701）、p-STAT3（Tyr705）和胶质纤维酸性蛋白在瘙痒病感染的脑中强烈表达。此外，我们发现瘙痒病感染的脑中p-STAT1和p-STAT3主要位于细胞核中。免疫组织化学结果显示，在瘙痒病感染的脑中许多反应性星形胶质细胞中，p-STAT1与LIF、CNTF和p-JAK2共定位。相比之下，在有限区域中相对较少的星形胶质细胞中发现了p-STAT3的免疫染色；在瘙痒病感染的脑的海马切片中，p-STAT3染色与p-JAK2染色融合。综上所述，我们的结果表明，瘙痒病感染的脑海马中的反应性星形胶质细胞中发生了JAK2-STAT1信号通路的激活。
