神戸大学附属図書館デジタルアーカイブ
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https://hdl.handle.net/20.500.14094/90008389
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2024-04-20
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90008389 (fulltext)
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メタデータID
90008389
アクセス権
open access
出版タイプ
Version of Record
タイトル
Mobilization efficiency is critically regulated by fat via marrow PPARδ
著者
Suzuki, Tomohide ; Ishii, Shinichi ; Shinohara, Masakazu ; Kawano, Yuko ; Wakahashi, Kanako ; Kawano, Hiroki ; Sada, Akiko ; Minagawa, Kentaro ; Hamada, Michito ; Takahashi, Satoru ; Furuyashiki, Tomoyuki ; Tan, Nguan Soon ; Matsui, Toshimitsu ; Katayama, Yoshio
著者名
Suzuki, Tomohide
著者名
Ishii, Shinichi
著者ID
A0846
研究者ID
1000080437483
KUID
https://kuid-rm-web.ofc.kobe-u.ac.jp/search/detail?systemId=7e44708e08ede856520e17560c007669
著者名
Shinohara, Masakazu
篠原, 正和
シノハラ, マサカズ
所属機関名
医学研究科
著者名
Kawano, Yuko
著者名
Wakahashi, Kanako
著者名
Kawano, Hiroki
著者名
Sada, Akiko
著者名
Minagawa, Kentaro
著者名
Hamada, Michito
著者ID
A0462
研究者ID
1000040311758
著者名
Takahashi, Satoru
高橋, 哲
タカハシ, サトル
所属機関名
医学部附属病院
著者ID
A0397
研究者ID
1000020362478
KUID
https://kuid-rm-web.ofc.kobe-u.ac.jp/search/detail?systemId=09b861d3853e7df7520e17560c007669
著者名
Furuyashiki, Tomoyuki
古屋敷, 智之
フルヤシキ, トモユキ
所属機関名
医学研究科
著者名
Tan, Nguan Soon
著者名
Matsui, Toshimitsu
著者ID
A1381
研究者ID
1000080397885
KUID
https://kuid-rm-web.ofc.kobe-u.ac.jp/search/detail?systemId=6d25cff00fdea105520e17560c007669
著者名
Katayama, Yoshio
片山, 義雄
カタヤマ, ヨシオ
所属機関名
医学部附属病院
収録物名
Haematologica
巻(号)
106(6)
ページ
1671-1683
出版者
Ferrata Storti Foundation
刊行日
2021-06
公開日
2021-07-02
抄録
The efficiency of mobilization of hematopoietic stem/progenitor cells from bone marrow into the circulation by granulocyte colony-stimulating factor (G-CSF) is extremely varied in humans and mice and a mechanistic explanation for poor mobilizers is lacking. A mechanism of regulating mobilization efficiency by dietary fat was assessed in mice. Compared to a normal diet, a fat-free diet for 2 weeks greatly increased mobilization. The bone marrow mRNA level of peroxisome proliferator-activated receptor delta (PPAR delta), a receptor for lipid mediators, was markedly upregulated by G-CSF in mice fed a normal diet and displayed a strong positive correlation with widely varied mobilization efficiency. It was hypothesized that the bone marrow fat ligand for PPAR delta might inhibit mobilization. A PPAR delta agonist inhibited mobilization in mice fed a normal diet and enhanced mobilization by a fat-free diet. Mice treated with a PPAR delta antagonist and chimeric mice with PPAR delta(+/-) bone marrow showed enhanced mobilization. Immunohistochemical staining and flow cytometry revealed that bone marrow PPAR delta expression was enhanced by G-CSF mainly in mature/immature neutrophils. Analysis of bone marrow lipid mediators revealed that G-CSF treatment and a fat-free diet resulted in exhaustion of omega 3-polyunsaturated fatty acids such as eicosapentaenoic acid. Eicosapentaenoic acid induced the upregulation of genes downstream of PPAR delta, such as Cpt1 alpha and Angptl4, in mature/immature neutrophils in vitro and inhibited enhanced mobilization in mice fed with a fat free diet in vivo. Treatment of wild-type mice with anti-Angptl4 antibody enhanced mobilization as well as bone marrow vascular permeability. Collectively, PPAR delta signaling in mature/immature bone marrow neutrophils induced by dietary fatty acids negatively regulates mobilization, at least partially, via Angptl4 production.
カテゴリ
医学研究科
医学部附属病院
学術雑誌論文
権利
© 2021 Ferrata Storti Foundation. Material published in Haematologica is covered by copyright. All rights are reserved to the Ferrata Storti Foundation.
Use of published material is allowed under the following terms and conditions: https://creativecommons.org/licenses/by-nc/4.0/legalcode. Copies of published material are allowed for personal or internal use. Sharing published material for non-commercial purposes is subject to the following conditions: https://creativecommons.org/licenses/by-nc/4.0/legalcode, sect. 3. Reproducing and sharing published material for commercial purposes is not allowed without permission in writing from the publisher.
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資源タイプ
journal article
言語
English (英語)
ISSN
0390-6078
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eISSN
1592-8721
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NCID
AA00660912
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関連情報
DOI
https://doi.org/10.3324/haematol.2020.265751
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