Down-regulation of Neuregulin2 (NRG2) following spinal cord injury in C57BL/6 mice: Its implications in therapeutic potential

Objective(s): This study aims to elucidate the alterations in Neuregulin 2 (NRG2) and its receptor ErbB4 following spinal cord injury (SCI), as well as to investigate the neuroprotective mechanisms of NRG2 in neurons. Materials and Methods: Dataset GSE93561 was analyzed to verify the changes of NRG2...

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Main Authors: Kai-Ye Hua, Yan-Jun Liu, Qi Ke, Quan Song, Shuai Zhang, Wei-Jiang Zhao
Format: Article
Language:English
Published: Mashhad University of Medical Sciences 2025-08-01
Series:Iranian Journal of Basic Medical Sciences
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Online Access:https://ijbms.mums.ac.ir/article_25920_a9565ec961a1a87b6d4063d614068a31.pdf
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author Kai-Ye Hua
Yan-Jun Liu
Qi Ke
Quan Song
Shuai Zhang
Wei-Jiang Zhao
author_facet Kai-Ye Hua
Yan-Jun Liu
Qi Ke
Quan Song
Shuai Zhang
Wei-Jiang Zhao
author_sort Kai-Ye Hua
collection DOAJ
description Objective(s): This study aims to elucidate the alterations in Neuregulin 2 (NRG2) and its receptor ErbB4 following spinal cord injury (SCI), as well as to investigate the neuroprotective mechanisms of NRG2 in neurons. Materials and Methods: Dataset GSE93561 was analyzed to verify the changes of NRG2-ErbB4 signaling pathway in mice following SCI. The levels of Iba-1 and NRG2 were analyzed by immunohistochemistry, and NRG2 and pErbB4 protein levels were detected by western blot. HT22 cells were scratched and treated with NRG2 dosed from 0–5 nM. Cell mobility was measured at the time point of 0, 24, and 48 hr after scratch. Additionally, western blot was used to detect the protein levels of pErbB4 and pAkt1 at 48 hr. Results: By analyzing dataset GSE93561, NRG1, NRG2, and NRG3 were found to be decreased to different degrees post-SCI in mice. The results of immunohistochemistry showed that the level of Iba-1 in the injured core area was significantly increased 8 weeks post-SCI. Western blot analysis showed that the protein levels of NRG2 and pErbB4 were decreased significantly post-SCI. NRG2 promoted HT22 cell migration and dose-dependently increased pErbB4 and pAkt1 protein levels at doses ranging from 0-5 nM. Conclusion: The NRG2-ErbB4 signaling pathway was inhibited after SCI in mice. NRG2 promotes the healing of HT22 cells after scratch injury, and the mechanism of NRG2 in the treatment of SCI may be ascribed to the activation of PI3K-Akt signaling pathways downstream to NRG2.
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spelling doaj-art-ea2ba4252d8b4a23b5dafdfc48fde3762025-08-20T03:08:33ZengMashhad University of Medical SciencesIranian Journal of Basic Medical Sciences2008-38662008-38742025-08-012881075108110.22038/ijbms.2025.83787.1813125920Down-regulation of Neuregulin2 (NRG2) following spinal cord injury in C57BL/6 mice: Its implications in therapeutic potentialKai-Ye Hua0Yan-Jun Liu1Qi Ke2Quan Song3Shuai Zhang4Wei-Jiang Zhao5Wuxi School of Medicine, Jiangnan University, Wuxi 214122, Jiangsu, P.R. ChinaWuxi School of Medicine, Jiangnan University, Wuxi 214122, Jiangsu, P.R. ChinaWuxi School of Medicine, Jiangnan University, Wuxi 214122, Jiangsu, P.R. ChinaWuxi School of Medicine, Jiangnan University, Wuxi 214122, Jiangsu, P.R. ChinaWuxi School of Medicine, Jiangnan University, Wuxi 214122, Jiangsu, P.R. ChinaWuxi School of Medicine, Jiangnan University, Wuxi 214122, Jiangsu, P.R. ChinaObjective(s): This study aims to elucidate the alterations in Neuregulin 2 (NRG2) and its receptor ErbB4 following spinal cord injury (SCI), as well as to investigate the neuroprotective mechanisms of NRG2 in neurons. Materials and Methods: Dataset GSE93561 was analyzed to verify the changes of NRG2-ErbB4 signaling pathway in mice following SCI. The levels of Iba-1 and NRG2 were analyzed by immunohistochemistry, and NRG2 and pErbB4 protein levels were detected by western blot. HT22 cells were scratched and treated with NRG2 dosed from 0–5 nM. Cell mobility was measured at the time point of 0, 24, and 48 hr after scratch. Additionally, western blot was used to detect the protein levels of pErbB4 and pAkt1 at 48 hr. Results: By analyzing dataset GSE93561, NRG1, NRG2, and NRG3 were found to be decreased to different degrees post-SCI in mice. The results of immunohistochemistry showed that the level of Iba-1 in the injured core area was significantly increased 8 weeks post-SCI. Western blot analysis showed that the protein levels of NRG2 and pErbB4 were decreased significantly post-SCI. NRG2 promoted HT22 cell migration and dose-dependently increased pErbB4 and pAkt1 protein levels at doses ranging from 0-5 nM. Conclusion: The NRG2-ErbB4 signaling pathway was inhibited after SCI in mice. NRG2 promotes the healing of HT22 cells after scratch injury, and the mechanism of NRG2 in the treatment of SCI may be ascribed to the activation of PI3K-Akt signaling pathways downstream to NRG2.https://ijbms.mums.ac.ir/article_25920_a9565ec961a1a87b6d4063d614068a31.pdfc57bl/6 mousemigrationnerve regenerationnrg2pi3k-aktspinal cord injury (sci)
spellingShingle Kai-Ye Hua
Yan-Jun Liu
Qi Ke
Quan Song
Shuai Zhang
Wei-Jiang Zhao
Down-regulation of Neuregulin2 (NRG2) following spinal cord injury in C57BL/6 mice: Its implications in therapeutic potential
Iranian Journal of Basic Medical Sciences
c57bl/6 mouse
migration
nerve regeneration
nrg2
pi3k-akt
spinal cord injury (sci)
title Down-regulation of Neuregulin2 (NRG2) following spinal cord injury in C57BL/6 mice: Its implications in therapeutic potential
title_full Down-regulation of Neuregulin2 (NRG2) following spinal cord injury in C57BL/6 mice: Its implications in therapeutic potential
title_fullStr Down-regulation of Neuregulin2 (NRG2) following spinal cord injury in C57BL/6 mice: Its implications in therapeutic potential
title_full_unstemmed Down-regulation of Neuregulin2 (NRG2) following spinal cord injury in C57BL/6 mice: Its implications in therapeutic potential
title_short Down-regulation of Neuregulin2 (NRG2) following spinal cord injury in C57BL/6 mice: Its implications in therapeutic potential
title_sort down regulation of neuregulin2 nrg2 following spinal cord injury in c57bl 6 mice its implications in therapeutic potential
topic c57bl/6 mouse
migration
nerve regeneration
nrg2
pi3k-akt
spinal cord injury (sci)
url https://ijbms.mums.ac.ir/article_25920_a9565ec961a1a87b6d4063d614068a31.pdf
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