JAK-STAT signaling pathway mediates astrogliosis in brains of scrapie-infected mice.
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.
Na
Yeo-Jung
YJ
Ilsong Institute of Life Science, College of Medicine, Hallym University, Anyang, Gyeonggi-do, South Korea.
Jin
Jae-Kwang
JK
Kim
Jae-Il
JI
Choi
Eun-Kyoung
EK
Carp
Richard I
RI
Kim
Yong-Sun
YS
D000818:Animals; D015153:Blotting, Western; D001921:Brain / Q000473:pathology*; D020934:Ciliary Neurotrophic Factor / Q000096:biosynthesis / Q000235:genetics; D005911:Gliosis / Q000473:pathology*; D006624:Hippocampus / Q000473:pathology; D007150:Immunohistochemistry; D053612:Janus Kinases / Q000502:physiology*; D053605:Leukemia Inhibitory Factor / Q000096:biosynthesis / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D010766:Phosphorylation; D021381:Protein Transport; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050791:STAT Transcription Factors / Q000502:physiology*; D012608:Scrapie / Q000473:pathology*; D015398:Signal Transduction / Q000502:physiology*; D013347:Subcellular Fractions / Q000473:pathology
D020934:Ciliary Neurotrophic Factor; D053605:Leukemia Inhibitory Factor; D050791:STAT Transcription Factors; D053612:Janus Kinases