Open Access

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

  • Authors:
    • Ji‑Yang An
    • Hong‑Gang Pang
    • Ting‑Qin Huang
    • Jin‑Ning Song
    • Dan‑Dong Li
    • Yong‑Lin Zhao
    • Xu‑Dong Ma
  • View Affiliations

  • Published online on: November 22, 2017     https://doi.org/10.3892/etm.2017.5539
  • Pages: 1330-1338
  • Copyright: © An et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

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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February 2018
Volume 15 Issue 2

Print ISSN: 1792-0981
Online ISSN:1792-1015

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APA
An, J., Pang, H., Huang, T., Song, J., Li, D., Zhao, Y., & Ma, X. (2018). AG490 ameliorates early brain injury via inhibition of JAK2/STAT3‑mediated regulation of HMGB1 in subarachnoid hemorrhage. Experimental and Therapeutic Medicine, 15, 1330-1338. https://doi.org/10.3892/etm.2017.5539
MLA
An, J., Pang, H., Huang, T., Song, J., Li, D., Zhao, Y., Ma, X."AG490 ameliorates early brain injury via inhibition of JAK2/STAT3‑mediated regulation of HMGB1 in subarachnoid hemorrhage". Experimental and Therapeutic Medicine 15.2 (2018): 1330-1338.
Chicago
An, J., Pang, H., Huang, T., Song, J., Li, D., Zhao, Y., Ma, X."AG490 ameliorates early brain injury via inhibition of JAK2/STAT3‑mediated regulation of HMGB1 in subarachnoid hemorrhage". Experimental and Therapeutic Medicine 15, no. 2 (2018): 1330-1338. https://doi.org/10.3892/etm.2017.5539