title: Overexpression of SOCS3 inhibits astrogliogenesis and promotes maintenance of neural stem cells.
abstract: To investigate the effects of suppressors of cytokine signaling 3 (SOCS3) on neural stem cell fate, stem cells were infected with an adenoviral vector expressing SOCS3. Three days later, western blot analysis and immunocytochemical analysis revealed that the protein level of MAP2 and the number of MAP2-positive cells were significantly increased in SOCS3-transfected cells, whereas the protein level of GFAP and the number of GFAP-positive cells were significantly decreased. Furthermore, promoter assay revealed a significant reduction in the transcriptional level of signal transducer and activator of transcription 3 (Stat3) in the transfected cells. In addition, the mRNA levels of Notch family member (notch1) and inhibitory basic helix-loop-helix (bHLH) factors (hes5 and id3) were significantly up-regulated 1 day after overexpression of SOCS3. Three days after transfection, the mRNA level of hes5 was significantly decreased, whereas that of notch1 was still up-regulated. Moreover, all of SOCS3-positive cells expressed Nestin protein but did not express MAP2 or GFAP proteins. These data indicate that overexpression of SOCS3 induced neurogenesis and inhibited astrogliogenesis in neural stem cells. Our data also show that SOCS3 promoted maintenance of neural stem cells.
authors.affiliation: Department of Functional Histology, Ehime Graduate University School of Medicine, Toon, Ehime, Japan.
authors.forename: Fang
authors.initials: F
authors.lastname: Cao
authors.forename: Ryuji
authors.initials: R
authors.lastname: Hata
authors.forename: Pengxiang
authors.initials: P
authors.lastname: Zhu
authors.forename: Yong-Jie
authors.initials: YJ
authors.lastname: Ma
authors.forename: Junya
authors.initials: J
authors.lastname: Tanaka
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Hanakawa
authors.forename: Koji
authors.initials: K
authors.lastname: Hashimoto
authors.forename: Michio
authors.initials: M
authors.lastname: Niinobe
authors.forename: Kazuaki
authors.initials: K
authors.lastname: Yoshikawa
authors.forename: Masahiro
authors.initials: M
authors.lastname: Sakanaka
mesh_terms: D000256:Adenoviridae / Q000378:metabolism; D001253:Astrocytes / Q000187:drug effects*; D002454:Cell Differentiation / Q000187:drug effects; D005822:Genetic Vectors; D005904:Glial Fibrillary Acidic Protein / Q000096:biosynthesis; D018257:Helix-Loop-Helix Motifs / Q000235:genetics; D006801:Humans; D015151:Immunoblotting; D007150:Immunohistochemistry; D007961:Leukocyte Migration-Inhibitory Factors / Q000494:pharmacology; D008156:Luciferases / Q000378:metabolism; D009474:Neurons / Q000187:drug effects*; D011401:Promoter Regions, Genetic / Q000235:genetics; D051881:Receptor, Notch1 / Q000096:biosynthesis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050796:STAT3 Transcription Factor / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology; D013234:Stem Cells / Q000187:drug effects*; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000096:biosynthesis* / Q000235:genetics*; D015854:Up-Regulation
chemical_list: D005904:Glial Fibrillary Acidic Protein; D007961:Leukocyte Migration-Inhibitory Factors; D051881:Receptor, Notch1; C106644:SOCS3 protein, human; D050796:STAT3 Transcription Factor; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D008156:Luciferases