Effect of Progranulin on Proliferation and Differentiation of Neural Stem/Progenitor Cells after Oxygen/Glucose Deprivation
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...
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MDPI AG
2022-02-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/23/4/1949 |
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| author | Ichiro Horinokita Hideki Hayashi Takamasa Nagatomo Yuna Fushiki Yui Iwatani Norio Takagi |
| author_facet | Ichiro Horinokita Hideki Hayashi Takamasa Nagatomo Yuna Fushiki Yui Iwatani Norio Takagi |
| author_sort | Ichiro Horinokita |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-09T21:45:41Z |
| format | Article |
| id | doaj.art-0d3ea6dbb30c49bbbf1417311aeff021 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T21:45:41Z |
| publishDate | 2022-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-0d3ea6dbb30c49bbbf1417311aeff0212023-11-23T20:17:07ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-02-01234194910.3390/ijms23041949Effect of Progranulin on Proliferation and Differentiation of Neural Stem/Progenitor Cells after Oxygen/Glucose DeprivationIchiro Horinokita0Hideki Hayashi1Takamasa Nagatomo2Yuna Fushiki3Yui Iwatani4Norio Takagi5Department of Applied Biochemistry, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji-shi, Hachioji 192-0392, JapanDepartment of Applied Biochemistry, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji-shi, Hachioji 192-0392, JapanDepartment of Applied Biochemistry, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji-shi, Hachioji 192-0392, JapanDepartment of Applied Biochemistry, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji-shi, Hachioji 192-0392, JapanDepartment of Applied Biochemistry, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji-shi, Hachioji 192-0392, JapanDepartment of Applied Biochemistry, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji-shi, Hachioji 192-0392, JapanWe 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.https://www.mdpi.com/1422-0067/23/4/1949cerebral ischemiaprogranulinneural stem/progenitor cellsAkt/GSK-3βneurite outgrowth |
| spellingShingle | Ichiro Horinokita Hideki Hayashi Takamasa Nagatomo Yuna Fushiki Yui Iwatani Norio Takagi Effect of Progranulin on Proliferation and Differentiation of Neural Stem/Progenitor Cells after Oxygen/Glucose Deprivation International Journal of Molecular Sciences cerebral ischemia progranulin neural stem/progenitor cells Akt/GSK-3β neurite outgrowth |
| title | Effect of Progranulin on Proliferation and Differentiation of Neural Stem/Progenitor Cells after Oxygen/Glucose Deprivation |
| title_full | Effect of Progranulin on Proliferation and Differentiation of Neural Stem/Progenitor Cells after Oxygen/Glucose Deprivation |
| title_fullStr | Effect of Progranulin on Proliferation and Differentiation of Neural Stem/Progenitor Cells after Oxygen/Glucose Deprivation |
| title_full_unstemmed | Effect of Progranulin on Proliferation and Differentiation of Neural Stem/Progenitor Cells after Oxygen/Glucose Deprivation |
| title_short | Effect of Progranulin on Proliferation and Differentiation of Neural Stem/Progenitor Cells after Oxygen/Glucose Deprivation |
| title_sort | effect of progranulin on proliferation and differentiation of neural stem progenitor cells after oxygen glucose deprivation |
| topic | cerebral ischemia progranulin neural stem/progenitor cells Akt/GSK-3β neurite outgrowth |
| url | https://www.mdpi.com/1422-0067/23/4/1949 |
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