Cargando…
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...
Autores principales: | , , , , , , |
---|---|
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 |
_version_ | 1783293757139976192 |
---|---|
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. |
format | Online Article Text |
id | pubmed-5774435 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | D.A. Spandidos |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT anjiyang ag490amelioratesearlybraininjuryviainhibitionofjak2stat3mediatedregulationofhmgb1insubarachnoidhemorrhage AT panghonggang ag490amelioratesearlybraininjuryviainhibitionofjak2stat3mediatedregulationofhmgb1insubarachnoidhemorrhage AT huangtingqin ag490amelioratesearlybraininjuryviainhibitionofjak2stat3mediatedregulationofhmgb1insubarachnoidhemorrhage AT songjinning ag490amelioratesearlybraininjuryviainhibitionofjak2stat3mediatedregulationofhmgb1insubarachnoidhemorrhage AT lidandong ag490amelioratesearlybraininjuryviainhibitionofjak2stat3mediatedregulationofhmgb1insubarachnoidhemorrhage AT zhaoyonglin ag490amelioratesearlybraininjuryviainhibitionofjak2stat3mediatedregulationofhmgb1insubarachnoidhemorrhage AT maxudong ag490amelioratesearlybraininjuryviainhibitionofjak2stat3mediatedregulationofhmgb1insubarachnoidhemorrhage |