Upregulation of gp130 and STAT3 activation in the rat hippocampus following transient forebrain ischemia.
To determine whether the pathophysiological processes after transient forebrain ischemia are mediated via a signal pathway involving gp130 (a signal transducer for the interleukin-6 family), we analyzed changes in the expression of gp130 and its downstream transcription factor, signal transducer and activator of transcription factor 3 (STAT3), in the rat hippocampus of a four-vessel occlusive ischemia model. Expression of gp130 mRNA was restricted to neurons of the pyramidal cell and granule cell layers in control animals. Four hours after ischemic injury, astrocytes expressed gp130 mRNA. Expression of gp130 increased preferentially in the CA1 and dentate hilar regions, and was maintained for at least 2 weeks. Increase in gp130 expression was accompanied by the activation of STAT3 following ischemic injury. Four hours after injury, STAT3 and phosphorylated STAT3 (pSTAT3) were observed in the nuclei of the dentate hilar region, and sequentially in the CA1 region at day 1. By day 3, STAT3 immunoreactivity markedly increased in these areas, where small cells with the morphology of astrocytes showed nuclear and cytoplasmic STAT3 and nuclear pSTAT3 immunoreactivities. These patterns were especially maintained in the CA1 area until 14 days of reperfusion. Double-labeling experiments revealed that the cells expressing STAT3 and pSTAT3 were glial fibrillary acidic protein-expressing reactive astrocytes. These results show a coordinated and long-lasting upregulation of gp130 mRNA and STAT3 activation in reactive astrocytes of the postischemic hippocampus, indicating that they may be involved in the astrocytic response to an ischemic insult.
Choi
Jeong-Sun
JS
Department of Anatomy, College of Medicine, Catholic University of Korea, Seoul, Korea.
Kim
Seong Yun
SY
Cha
Jung-Ho
JH
Choi
Yun-Sik
YS
Sung
Ki-Wug
KW
Oh
Seong Taek
ST
Kim
Ok Nyu
ON
Chung
Jin-Woong
JW
Chun
Myung-Hoon
MH
Lee
Sang Bok
SB
Lee
Mun-Yong
MY
D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism*; D001253:Astrocytes / Q000378:metabolism*; D050822:Cytokine Receptor gp130; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D015870:Gene Expression / Q000502:physiology; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism*; D002546:Ischemic Attack, Transient / Q000378:metabolism*; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D017966:Pyramidal Cells / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D050796:STAT3 Transcription Factor; D020521:Stroke / Q000378:metabolism; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation / Q000502:physiology
D015703:Antigens, CD; D004268:DNA-Binding Proteins; C494201:Il6st protein, rat; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D050796:STAT3 Transcription Factor; C494088:Stat3 protein, rat; D015534:Trans-Activators; D050822:Cytokine Receptor gp130