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AG490 ameliorates early brain injury via inhibition of JAK2/STAT3-mediated regulation of HMGB1 in subarachnoid hemorrhage

High mobility group box 1 (HMGB1) is a classic damage-associated molecular pattern that has an important role in the pathological inflammatory response. In vitro studies have demonstrated that the Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) signaling pathway is i...

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Autores principales: An, Ji-Yang, Pang, Hong-Gang, Huang, Ting-Qin, Song, Jin-Ning, Li, Dan-Dong, Zhao, Yong-Lin, Ma, Xu-Dong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: D.A. Spandidos 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5774435/
https://www.ncbi.nlm.nih.gov/pubmed/29434719
http://dx.doi.org/10.3892/etm.2017.5539
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author An, Ji-Yang
Pang, Hong-Gang
Huang, Ting-Qin
Song, Jin-Ning
Li, Dan-Dong
Zhao, Yong-Lin
Ma, Xu-Dong
author_facet An, Ji-Yang
Pang, Hong-Gang
Huang, Ting-Qin
Song, Jin-Ning
Li, Dan-Dong
Zhao, Yong-Lin
Ma, Xu-Dong
author_sort An, Ji-Yang
collection PubMed
description High mobility group box 1 (HMGB1) is a classic damage-associated molecular pattern that has an important role in the pathological inflammatory response. In vitro studies have demonstrated that the Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) signaling pathway is involved in the regulation of HMGB1 expression, mediating the inflammatory response. Therefore, the purpose of the present study was to evaluate JAK2/STAT3 pathway involvement in the subarachnoid hemorrhage (SAH)-dependent regulation of HMGB1, using an in vivo rat model. A SAH model was established by endovascular perforation. Western blotting, immunohistochemistry and immunofluorescence were used to analyze HMGB1 expression after SAH. In addition, the effects of AG490 after SAH on JAK2/STAT3 phosphorylation, HMGB1 expression and brain damage were evaluated. The results of the present study demonstrated that JAK2/STAT3 was significantly phosphorylated (P<0.05) and the total HMGB1 protein level was significantly increased (P<0.05) after SAH. In addition, the cytosolic HMGB1 level after SAH demonstrated an initial increase followed by a decrease to the control level, while the nuclear HMGB1 level after SAH demonstrated the opposite trend, with an initial decrease and subsequent increase. AG490 administration after SAH significantly inhibited JAK2/STAT3 phosphorylation (P<0.05), suppressed the expression and translocation of HMGB1, reduced cortical apoptosis, brain edema and neurological deficits. These results demonstrated the involvement of the JAK2/STAT3 pathway in HMGB1 regulation after SAH.
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spelling pubmed-57744352018-02-12 AG490 ameliorates early brain injury via inhibition of JAK2/STAT3-mediated regulation of HMGB1 in subarachnoid hemorrhage An, Ji-Yang Pang, Hong-Gang Huang, Ting-Qin Song, Jin-Ning Li, Dan-Dong Zhao, Yong-Lin Ma, Xu-Dong Exp Ther Med Articles High mobility group box 1 (HMGB1) is a classic damage-associated molecular pattern that has an important role in the pathological inflammatory response. In vitro studies have demonstrated that the Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) signaling pathway is involved in the regulation of HMGB1 expression, mediating the inflammatory response. Therefore, the purpose of the present study was to evaluate JAK2/STAT3 pathway involvement in the subarachnoid hemorrhage (SAH)-dependent regulation of HMGB1, using an in vivo rat model. A SAH model was established by endovascular perforation. Western blotting, immunohistochemistry and immunofluorescence were used to analyze HMGB1 expression after SAH. In addition, the effects of AG490 after SAH on JAK2/STAT3 phosphorylation, HMGB1 expression and brain damage were evaluated. The results of the present study demonstrated that JAK2/STAT3 was significantly phosphorylated (P<0.05) and the total HMGB1 protein level was significantly increased (P<0.05) after SAH. In addition, the cytosolic HMGB1 level after SAH demonstrated an initial increase followed by a decrease to the control level, while the nuclear HMGB1 level after SAH demonstrated the opposite trend, with an initial decrease and subsequent increase. AG490 administration after SAH significantly inhibited JAK2/STAT3 phosphorylation (P<0.05), suppressed the expression and translocation of HMGB1, reduced cortical apoptosis, brain edema and neurological deficits. These results demonstrated the involvement of the JAK2/STAT3 pathway in HMGB1 regulation after SAH. D.A. Spandidos 2018-02 2017-11-22 /pmc/articles/PMC5774435/ /pubmed/29434719 http://dx.doi.org/10.3892/etm.2017.5539 Text en Copyright: © An et al. This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
spellingShingle Articles
An, Ji-Yang
Pang, Hong-Gang
Huang, Ting-Qin
Song, Jin-Ning
Li, Dan-Dong
Zhao, Yong-Lin
Ma, Xu-Dong
AG490 ameliorates early brain injury via inhibition of JAK2/STAT3-mediated regulation of HMGB1 in subarachnoid hemorrhage
title AG490 ameliorates early brain injury via inhibition of JAK2/STAT3-mediated regulation of HMGB1 in subarachnoid hemorrhage
title_full AG490 ameliorates early brain injury via inhibition of JAK2/STAT3-mediated regulation of HMGB1 in subarachnoid hemorrhage
title_fullStr AG490 ameliorates early brain injury via inhibition of JAK2/STAT3-mediated regulation of HMGB1 in subarachnoid hemorrhage
title_full_unstemmed AG490 ameliorates early brain injury via inhibition of JAK2/STAT3-mediated regulation of HMGB1 in subarachnoid hemorrhage
title_short AG490 ameliorates early brain injury via inhibition of JAK2/STAT3-mediated regulation of HMGB1 in subarachnoid hemorrhage
title_sort ag490 ameliorates early brain injury via inhibition of jak2/stat3-mediated regulation of hmgb1 in subarachnoid hemorrhage
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5774435/
https://www.ncbi.nlm.nih.gov/pubmed/29434719
http://dx.doi.org/10.3892/etm.2017.5539
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