Leukemia Inhibitory Factor Contributes to Reactive Astrogliosis via Activation of Signal Transducer and Activator of Transcription 3 Signaling after Intracerebral Hemorrhage in Rats.
Reactive astrogliosis has occurred after intracerebral hemorrhage (ICH). Leukemia inhibitory factor (LIF) can act as a modulator for glial gene expression. Signal transducer and activator of transcription 3 (STAT3) is a critical regulator of reactive astrogliosis. The present study tested whether endogenous LIF acted on ICH-induced reactive astrogliosis via the STAT3 signaling pathway. Rats were divided into three experimental groups: 1) Rats received either an ICH or a needle insertion (sham), 2) Rats received 100 ng LIF or an equal volume of phosphate-buffered saline (PBS) by direct infusion into the lateral ventricle (LV) after ICH, and 3) AG490 (0.25 mg/kg) was injected into the LV to block STAT3 signaling. Brains were perfused to identify proliferating cell nuclear antigen (PCNA)+/glial fibrillary acidic protein (GFAP)+nuclei. The expression of GFAP, LIF, LIF receptor (LIFR), glycoprotein 130 (gp130), and phospho-STAT3 (p-STAT3) was evaluated by immunohistochemistry and Western blot, respectively. After ICH, the number of the PCNA+/GFAP+nuclei and the expression of GFAP, LIF, LIFR, gp130, and p-STAT3 were increased. Moreover, LIF increased the number of PCNA+/GFAP+nuclei and the expression of GFAP, LIFR, gp130, and p-STAT3. The number of PCNA+/ GFAP+nuclei and GFAP protein levels were attenuated markedly after inhibition of p-STAT3. Together, these data suggest that LIF contributes to ICH-related reactive astrogliosis via activation of STAT3 signaling.
1 The SATCM Key Lab of Chinese Gan, Central South University, Changsha , Hunan, P. R. China .|2 Institute of Neurology, China Three Gorges University , Yichang, Hubei, P. R. China .|3 Department of Neurology, China Three Gorges University , Yichang, Hubei, P. R. China .
Hua-Jun
HJ
Zhou
2 Institute of Neurology, China Three Gorges University , Yichang, Hubei, P. R. China .|3 Department of Neurology, China Three Gorges University , Yichang, Hubei, P. R. China .
Xi
X
Yang
1 The SATCM Key Lab of Chinese Gan, Central South University, Changsha , Hunan, P. R. China .|4 Institute of Integrative Medicine, Central South University, Changsha , Hunan, P. R. China .
Han-Jin
HJ
Cui
1 The SATCM Key Lab of Chinese Gan, Central South University, Changsha , Hunan, P. R. China .|4 Institute of Integrative Medicine, Central South University, Changsha , Hunan, P. R. China .
Tao
T
Tang
5 Department of Intensive Care Unit, The First College of Clinical Medical Sciences, China Three Gorges University , Yichang, Hubei, P. R. China .
Jian-Hua
JH
Zhong
1 The SATCM Key Lab of Chinese Gan, Central South University, Changsha , Hunan, P. R. China .|4 Institute of Integrative Medicine, Central South University, Changsha , Hunan, P. R. China .
Jie-Kun
JK
Luo
6 Department of Hyperbaric Oxygen, Xiangya Hospital, Central South University, Changsha , Hunan, P. R. China .
A-Li
AL
Yang
2 Institute of Neurology, China Three Gorges University , Yichang, Hubei, P. R. China .|3 Department of Neurology, China Three Gorges University , Yichang, Hubei, P. R. China .
Qi-Mei
QM
Zhang
2 Institute of Neurology, China Three Gorges University , Yichang, Hubei, P. R. China .|3 Department of Neurology, China Three Gorges University , Yichang, Hubei, P. R. China .
Jing-Hua
JH
Zhou
2 Institute of Neurology, China Three Gorges University , Yichang, Hubei, P. R. China .|3 Department of Neurology, China Three Gorges University , Yichang, Hubei, P. R. China .
Qiang
Q
Zhang
D000818:Animals; D002543:Cerebral Hemorrhage / Q000378:metabolism*; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000494:pharmacology; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D005911:Gliosis / Q000378:metabolism*; D053605:Leukemia Inhibitory Factor / Q000378:metabolism*; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D050796:STAT3 Transcription Factor / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D020032:Tyrphostins / Q000008:administration & dosage / Q000494:pharmacology
D004791:Enzyme Inhibitors; C000614142:Gfap protein, rat; D005904:Glial Fibrillary Acidic Protein; D053605:Leukemia Inhibitory Factor; D018809:Proliferating Cell Nuclear Antigen; D050796:STAT3 Transcription Factor; D020032:Tyrphostins; C095512:alpha-cyano-(3,4-dihydroxy)-N-benzylcinnamide
ICH; LIF; STAT3 signaling; glial scar; reactive astrogliosis