Astrocytic endothelin-1 overexpression promotes neural progenitor cells proliferation and differentiation into astrocytes via the Jak2/Stat3 pathway after stroke
机构：[1]Department of Neurology, Guangdong Provincial Hospital of TraditionalChinese Medicine, 111 Dade Road, Guangzhou 510120, China[2]Faculty ofMedicine, Macau University of Science and Technology, Macau, China[3]School of Biomedical Sciences, The University of Hong Kong, HKSAR, China[4]The Second Affiliated Hospital of Guangzhou University of ChineseMedicine, 12 Jichang Road, Guangzhou 510405, China[5]GuangdongProvincial Chinese Emergency Key Laboratory, Guangzhou 510120, China[6]State Key Laboratory of Dampness Syndrome of Traditional ChineseMedicine, Guangzhou 510120, China[7]Department of Anatomy, Zhong ShanSchool of Medicine, Sun Yat-Sen University, Guangdong Province,Guangzhou, China
Background Endothelin-1 (ET-1) is synthesized and upregulated in astrocytes under stroke. We previously demonstrated that transgenic mice over-expressing astrocytic ET-1 (GET-1) displayed more severe neurological deficits characterized by a larger infarct after transient middle cerebral artery occlusion (tMCAO). ET-1 is a known vasoconstrictor, mitogenic, and a survival factor. However, it is unclear whether the observed severe brain damage in GET-1 mice post stroke is due to ET-1 dysregulation of neurogenesis by altering the stem cell niche. Methods Non-transgenic (Ntg) and GET-1 mice were subjected to tMCAO with 1 h occlusion followed by long-term reperfusion (from day 1 to day 28). Neurological function was assessed using a four-point scale method. Infarct area and volume were determined by 2,3,5-triphenyltetra-zolium chloride staining. Neural stem cell (NSC) proliferation and migration in subventricular zone (SVZ) were evaluated by immunofluorescence double labeling of bromodeoxyuridine (BrdU), Ki67 and Sox2, Nestin, and Doublecortin (DCX). NSC differentiation in SVZ was evaluated using the following immunofluorescence double immunostaining: BrdU and neuron-specific nuclear protein (NeuN), BrdU and glial fibrillary acidic protein (GFAP). Phospho-Stat3 (p-Stat3) expression detected by Western-blot and immunofluorescence staining. Results GET-1 mice displayed a more severe neurological deficit and larger infarct area after tMCAO injury. There was a significant increase of BrdU-labeled progenitor cell proliferation, which co-expressed with GFAP, at SVZ in the ipsilateral side of the GET-1 brain at 28 days after tMCAO. p-Stat3 expression was increased in both Ntg and GET-1 mice in the ischemia brain at 7 days after tMCAO. p-Stat3 expression was significantly upregulated in the ipsilateral side in the GET-1 brain than that in the Ntg brain at 7 days after tMCAO. Furthermore, GET-1 mice treated with AG490 (a JAK2/Stat3 inhibitor) sh owed a significant reduction in neurological deficit along with reduced infarct area and dwarfed astrocytic differentiation in the ipsilateral brain after tMCAO. Conclusions The data indicate that astrocytic endothelin-1 overexpression promotes progenitor stem cell proliferation and astr ocytic differentiation via the Jak2/Stat3 pathway.
基金：
National Natural Science
Foundation of China, No. 81303115, 81774042, and 81771353; the Natural
Science Foundation of Guangdong Province of China, No. S2013040016915;
the Science and Technology Program of Guangzhou City of China, No.
201604020003; the Pearl River S & T Nova Program of Guangzhou,
No.201806010025, the Postdoctoral Foundation of China, No. BBK42913K09,
201003345, and BBH429151701; Hong Kong Scholar Program, the Specialty
Program of Guangdong Province Hospital of Traditional Chinese Medicine of
China, No. YN2016MJ07, 2015KT1294, YN2015MS02, and YN2018ZD07 and
the Youth Pilot Project of Chinese Society of Traditional Chinese Medicine
CACM-2018-QNRC2-C09.
第一作者机构：[1]Department of Neurology, Guangdong Provincial Hospital of TraditionalChinese Medicine, 111 Dade Road, Guangzhou 510120, China[3]School of Biomedical Sciences, The University of Hong Kong, HKSAR, China[4]The Second Affiliated Hospital of Guangzhou University of ChineseMedicine, 12 Jichang Road, Guangzhou 510405, China[5]GuangdongProvincial Chinese Emergency Key Laboratory, Guangzhou 510120, China[6]State Key Laboratory of Dampness Syndrome of Traditional ChineseMedicine, Guangzhou 510120, China
通讯作者：
通讯机构：[1]Department of Neurology, Guangdong Provincial Hospital of TraditionalChinese Medicine, 111 Dade Road, Guangzhou 510120, China[2]Faculty ofMedicine, Macau University of Science and Technology, Macau, China[3]School of Biomedical Sciences, The University of Hong Kong, HKSAR, China[4]The Second Affiliated Hospital of Guangzhou University of ChineseMedicine, 12 Jichang Road, Guangzhou 510405, China[5]GuangdongProvincial Chinese Emergency Key Laboratory, Guangzhou 510120, China[6]State Key Laboratory of Dampness Syndrome of Traditional ChineseMedicine, Guangzhou 510120, China
推荐引用方式(GB/T 7714)：
Cheng Xiao,Yeung Patrick K. K.,Zhong Ke,et al.Astrocytic endothelin-1 overexpression promotes neural progenitor cells proliferation and differentiation into astrocytes via the Jak2/Stat3 pathway after stroke[J].JOURNAL OF NEUROINFLAMMATION.2019,16(1):doi:10.1186/s12974-019-1597-y.
APA：
Cheng, Xiao,Yeung, Patrick K. K.,Zhong, Ke,Zilundu, Prince L. M.,Zhou, Lihua&Chung, Sookja K..(2019).Astrocytic endothelin-1 overexpression promotes neural progenitor cells proliferation and differentiation into astrocytes via the Jak2/Stat3 pathway after stroke.JOURNAL OF NEUROINFLAMMATION,16,(1)
MLA：
Cheng, Xiao,et al."Astrocytic endothelin-1 overexpression promotes neural progenitor cells proliferation and differentiation into astrocytes via the Jak2/Stat3 pathway after stroke".JOURNAL OF NEUROINFLAMMATION 16..1(2019)
医学