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http://hdl.handle.net/10564/4441
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タイトル: | MEK inhibitor PD0325901 upregulates CD34 expression in endothelial cells via inhibition of ERK phosphorylation |
その他のタイトル: | MEK阻害剤PD0325901はERKリン酸化阻害を介して 内皮細胞におけるCD34発現を上昇させる |
著者: | Hosoda, Chihiro Mitani, Seiji Sakata, Asuka Kasuda, Shogo Onodera, Yu Takabayashi, Yoko Shima, Midori Tatsumi, Kohei |
キーワード: | CD34 Endothelial cell Endothelial progenitor cell PD0325901 Reprogramming |
発行日: | 2024年8月29日木曜日 |
出版者: | Elsevier |
引用: | Regenerative therapy. 2024 Aug, vol.26, p.654-662 |
抄録: | CD34-positive endothelial progenitor cells (EPCs) promote angiogenesis and are a promising
tool for regenerative cell therapy of ischemic diseases. However, the number and quality of CD34-positive cells decrease owing to various external and internal factors; thus, an efficient method is needed to establish CD34-positive EPCs. The generation of functional cells by reprogramming, that is, manipulating
cell fate via gene transfer and/or treatment with chemical compounds, has recently been reported.
Therefore, we aimed to generate CD34-positive cells by the reprogramming of endothelial cells (ECs).
Methods: Based on previous reports, seven candidate chemical compounds were selected to reprogram human umbilical vein ECs (HUVECs) to CD34-positive cells. Following stimulation with the chemical compounds, the expression of CD34 was evaluated using quantitative PCR, flow cytometry, and immunocytochemistry.
Results: HUVECs treated with the compounds exhibited increased CD34 expression. We cultured cells in alternate media lacking one of the seven compounds and found no CD34 expression in cells treated with PD0325901-free media, suggesting that PD0325901da MEK inhibitordmainly contributed to the increase
in CD34 expression. We found that 98% of cells were CD34-positive after PD0325901 treatment
alone for 7 d. Western blotting revealed that the phosphorylation of ERK was suppressed in PD0325901- treated cells. No upregulation of CD34 was observed in fibroblast cell lines, even after PD0325901 treatment. These results suggested that PD0325901 induces CD34-positive cells by inhibiting ERK phosphorylation in ECs.
Conclusions: CD34 expression was strongly induced in ECs by treatment with the MEK inhibitor PD0325901 in vitro. Our study provides a useful reference for the establishment of CD34-positive EPCs and will contribute to the development of regenerative therapies, especially for ischemic diseases. |
内容記述: | © 2024 The Author(s). Published by Elsevier BV on behalf of The Japanese Society for Regenerative
Medicine. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/
licenses/by-nc-nd/4.0/). |
URI: | http://hdl.handle.net/10564/4441 |
ISSN: | 2352-3204 |
DOI: | https://doi.org/10.1016/j.reth.2024.08.009 |
学位授与番号: | 24601甲第946号 |
学位授与年月日: | 2025-03-14 |
学位名: | 博士(医学) |
学位授与機関: | 奈良県立医科大学 |
出現コレクション: | 2024年度
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