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タイトル: Antagonist of sphingosine 1-phosphate receptor 3 reduces cold injury of rat donor hearts for transplantation
著者: Kanemitsu, Eisho
Zhao, Xiangdong
Iwaisako, Keiko
Inoue, Asuka  kyouindb  KAKEN_id  orcid https://orcid.org/0000-0003-0805-4049 (unconfirmed)
Takeuchi, Akihide
Yagi, Shintaro
Masumoto, Hidetoshi
Ohara, Hiroaki
Hosokawa, Motoyasu
Awaya, Tomonari
Aoki, Junken
Hatano, Etsuro
Uemoto, Shinji
Hagiwara, Masatoshi
著者名の別形: 金光, 瑛彰
趙, 向東
祝迫, 惠子
武内, 章英
八木, 真太郎
大原, 寛明
細川, 元靖
粟屋, 智就
波多野, 悦朗
上本, 伸二
萩原, 正敏
キーワード: organ transplantation
cold injury
organ preservation
sphingosine-1-phosphate (S1P)
S1P receptor (S1PR)
cold tolerance
hibernation
TOACH (Tolerant Adaptation toward Cooling as Hibernation)
発行日: May-2023
出版者: Elsevier BV
誌名: Translational Research
巻: 255
開始ページ: 26
終了ページ: 36
抄録: Cold storage is widely used to preserve an organ for transplantation; however, a long duration of cold storage negatively impacts graft function. Unfortunately, the mechanisms underlying cold exposure remain unclear. Based on the sphingosine-1-phosphate (S1P) signal involved in cold tolerance in hibernating mammals, we hypothesized that S1P signal blockage reduces damage from cold storage. We used an in vitro cold storage and rewarming model to evaluate cold injury and investigated the relationship between cold injury and S1P signal. Compounds affecting S1P receptors (S1PR) were screened for their protective effect in this model and its inhibitory effect on S1PRs was measured using the NanoLuc Binary Technology (NanoBiT)-β-arrestin recruitment assays. The effects of a potent antagonist were examined via heterotopic abdominal rat heart transplantation. The heart grafts were transplanted after 24-hour preservation and evaluated on day 7 after transplantation. Cold injury increased depending on the cold storage time and was induced by S1P. The most potent antagonist strongly suppressed cold injury consistent with the effect of S1P deprivation in vitro. In vivo, this antagonist enabled 24-hour preservation, and drastically improved the beating score, cardiac size, and serological markers. Pathological analysis revealed that it suppressed the interstitial edema, inflammatory cell infiltration, myocyte lesion, TUNEL-positive cell death, and fibrosis. In conclusion, S1PR3 antagonist reduced cold injury, extended the cold preservation time, and improved graft viability. Cold preservation strategies via S1P signaling may have clinical applications in organ preservation for transplantation and contribute to an increase in the donor pool.
著作権等: © 2022 The Authors. Published by Elsevier Inc.
This is an open access article under the CC BY-NC-ND license.
URI: http://hdl.handle.net/2433/284692
DOI(出版社版): 10.1016/j.trsl.2022.11.003
PubMed ID: 36347491
出現コレクション:学術雑誌掲載論文等

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