5-Aminolevulinic acid combined with sodium ferrous citrate (5-ALA/SFC) ameliorated liver injury in a murine acute graft-versus-host disease model by reducing inflammation responses through PGC1-alpha activation
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- Wang Zhidan
- Division of Transplantation Immunology, National Research Institute for Child Health and Development, Tokyo, Japan. Laboratory of Functional Morphology Graduate School of Human Health Sciences Tokyo Metropolitan University, Tokyo, Japan.
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- Ma Kuai
- Division of Transplantation Immunology, National Research Institute for Child Health and Development, Tokyo, Japan.
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- Liu Chi
- Division of Transplantation Immunology, National Research Institute for Child Health and Development, Tokyo, Japan.
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- Hu Xin
- Division of Transplantation Immunology, National Research Institute for Child Health and Development, Tokyo, Japan.
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- Que Weitao
- Division of Transplantation Immunology, National Research Institute for Child Health and Development, Tokyo, Japan.
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- Ito Hidenori
- SBI Pharmaceuticals Co., Ltd., Tokyo, Japan.
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- Takahashi Kiwamu
- SBI Pharmaceuticals Co., Ltd., Tokyo, Japan.
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- Nakajima Motowo
- SBI Pharmaceuticals Co., Ltd., Tokyo, Japan.
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- Tanaka Tohru
- SBI Pharmaceuticals Co., Ltd., Tokyo, Japan.
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- Ren Ke
- Project Division for Healthcare Innovation, Graduate School of Human Health Sciences, Tokyo Metropolitan University, Tokyo, Japan.
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- Guo Wen-Zhi
- Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
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- Yi Shuang-Qin
- Laboratory of Functional Morphology Graduate School of Human Health Sciences Tokyo Metropolitan University, Tokyo, Japan.
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- Li Xiao-Kang
- Division of Transplantation Immunology, National Research Institute for Child Health and Development, Tokyo, Japan. Project Division for Healthcare Innovation, Graduate School of Human Health Sciences, Tokyo Metropolitan University, Tokyo, Japan. Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
書誌事項
- タイトル別名
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- 5-Aminolevulinic acid combined with sodium ferrous citrate (5-ALA/SFC) ameliorated liver injury in a murine acute graft-versus-host disease model by reducing inflammation responses through PGC1-α activation
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抄録
<p>Acute graft-versus-host disease (aGvHD) remains lethal as a life-threatening complication after allogeneic hematopoietic stem cell transplantation (HSCT). Inflammatory responses play an important role in aGvHD. 5-Aminolevulinic acid combined with sodium ferrous citrate (5-ALA/SFC) has been widely reported to have a major effect on the anti-inflammatory response; however, these effects in aGvHD models have never been reported. In this study, a murine aGvHD model was developed by transferring spleen cells from donor B6/N (H-2kb) mice into recipient B6D2F1 (H-2kb/d) mice. In addition to evaluating manifestations in aGvHD mice, we analyzed the serum ALT/AST levels, liver pathological changes, infiltrating cells and mRNA expression of inflammation-related cytokines and chemokines. 5-ALA/SFC treatment significantly ameliorated liver injury due to aGvHD and decreased the population of liver-infiltrating T cells, resulting in a reduced expression of pro-inflammatory cytokines and chemokines. Furthermore, the mRNA expression proliferator-activated receptor-γcoactivator (PGC-1α) was enhanced, which might explain why 5-ALA/SFC treatment downregulates inflammatory signaling pathways. Our results indicated that 5-ALA/SFC can ameliorate liver injury induced by aGvHD through the activation of PGC-1α and modulation of the liver mRNA expression of inflammatory-related cytokines and chemokines. This may be a novel strategy for treating this disease.</p>
収録刊行物
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- Drug Discoveries & Therapeutics
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Drug Discoveries & Therapeutics 14 (6), 304-312, 2020-12-31
特定非営利活動法人 バイオ＆ソーシャル・サイエンス推進国際研究交流会