論文

国際誌
2022年2月9日

Effect of Progranulin on Proliferation and Differentiation of Neural Stem/Progenitor Cells after Oxygen/Glucose Deprivation.

International journal of molecular sciences
  • Ichiro Horinokita
  • ,
  • Hideki Hayashi
  • ,
  • Takamasa Nagatomo
  • ,
  • Yuna Fushiki
  • ,
  • Yui Iwatani
  • ,
  • Norio Takagi

23
4
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.3390/ijms23041949

We previously demonstrated that sivelestat, a selective neutrophil elastase inhibitor, attenuates the cleavage of progranulin (PGRN) and ischemia-induced cell injury in the brain. To obtain further insight into the role of PGRN, in the present study we evaluated the direct effects of sivelestat and recombinant PGRN (rPGRN) on the proliferation and differentiation of neural stem cells in cultures of neural stem/progenitor cells (NS/PC) under the ischemic condition in vitro. We demonstrated that oxygen/glucose deprivation (OGD)-induced cell proliferation of NS/PC was increased by rPGRN treatment. In addition, this increase was accompanied by increased phosphorylation of Akt and GSK-3β (Ser9) after OGD. But none of these responses occurred by treatment with sivelestat. Therefore, activation of the Akt/GSK-3β pathway could well be involved in this proliferative effect of rPGRN. Although OGD and reoxygenation-induced changes in the differentiation of NS/PC into neurons or astrocytes was not affected by treatment with rPGRN or sivelestat, it is noteworthy that rPGRN enhanced neurite outgrowth of β3-tubulin-positive neurons that had differentiated from the NS/PC. These findings suggest that enhancement of proliferation of endogenous NS/PC and neurite outgrowth of differentiated neurons from NS/PC by PGRN could be useful for a new therapeutic approach for cerebral ischemia.

リンク情報
DOI
https://doi.org/10.3390/ijms23041949
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/35216064
PubMed Central
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8879483
ID情報
  • DOI : 10.3390/ijms23041949
  • PubMed ID : 35216064
  • PubMed Central 記事ID : PMC8879483

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