Therapeutic Potential of the Prolyl Hydroxylase Inhibitor Roxadustat in a Mouse Hindlimb Lymphedema Model

Hoshino, Yoshitada; Osawa, Masayuki; Funayama, Emi; Ishikawa, Kosuke; Miura, Takahiro; Hojo, Masahiro; Yamamoto, Yuhei; Maeda, Taku

Therapeutic Potential of the Prolyl Hydroxylase Inhibitor Roxadustat in a Mouse Hindlimb Lymphedema Model

Hoshino, Yoshitada; Osawa, Masayuki; Funayama, Emi et al.

Lymphatic Research and Biology, 2023, 21(4), 372-380

Permalink : https://hdl.handle.net/2115/88778

このアイテムのアクセス数:651件（2026-03-11 20:47 集計）

閲覧可能ファイル

ファイル	フォーマット	サイズ	閲覧回数	説明
LRB_lrb.2022.0071	pdf	3.29 MB	459

論文情報

ファイル出力 EndNote Basic出力 Mendeley出力

アクセス権	open access
URI	https://hdl.handle.net/2115/88778
タイトル	Therapeutic Potential of the Prolyl Hydroxylase Inhibitor Roxadustat in a Mouse Hindlimb Lymphedema Model
著者	Hoshino, Yoshitada ; Osawa, Masayuki ; Funayama, Emi ; Ishikawa, Kosuke ; Miura, Takahiro ; Hojo, Masahiro ; Yamamoto, Yuhei ; Maeda, Taku
著者名 Hoshino, Yoshitada
e-Rad_Researcher 70625029 著者名 Osawa, Masayuki
e-Rad_Researcher 10533630 著者名 Funayama, Emi
e-Rad_Researcher 60791374 著者名 Ishikawa, Kosuke
著者名 Miura, Takahiro
著者名 Hojo, Masahiro
e-Rad_Researcher 70271674 著者名 Yamamoto, Yuhei
著者名 Maeda, Taku
言語	英語
キーワード	lymphedema
	roxadustat
	FG-4592
発行日	2023-08-01
収録物名	Lymphatic Research and Biology
巻(号)	21(4)
ページ	372-380
抄録	Background: Lymphedema is an intractable disease with no curative treatment available. Conservative treatment is the mainstay, and new drug treatment options are strongly needed. The purpose of this study was to investigate the effect of roxadustat, a prolyl-4-hydroxylase inhibitor, on lymphangiogenesis and its therapeutic effect on lymphedema in a radiation-free mouse hindlimb lymphedema model. Methods and Results: Male C57BL/6N mice (8–10 weeks old) were used for the lymphedema model. Mice were randomized to an experimental group receiving roxadustat or a control group. The circumferential ratio of the hindlimbs was evaluated, and lymphatic flow of the hindlimbs was compared by fluorescent lymphography up to 28 days postoperatively. The roxadustat group showed an early improvement in hindlimb circumference and stasis of lymphatic flow. The number and area of lymphatic vessels on postoperative day 7 were significantly larger and smaller, respectively, in the roxadustat group compared with the control group. Skin thickness and macrophage infiltration on postoperative day 7 were significantly reduced in the roxadustat group compared with the control group. The relative mRNA expression of hypoxia-inducible factor-1α (Hif-1α), vascular endothelial growth factor receptor-3 (VEGFR-3), vascular endothelial growth factor-C (VEGF-C), and Prospero homeobox 1 (Prox1) on postoperative day 4 was significantly higher in the roxadustat group compared with the control group. Conclusions: Roxadustat demonstrated a therapeutic effect in a murine model of hindlimb lymphedema through promotion of lymphangiogenesis through the activation of HIF-1α, VEGF-C, VEGFR-3, and Prox1, suggesting the potential of roxadustat as a therapeutic option in lymphedema.
資源タイプ	学術雑誌論文
出版タイプ	Accepted Manuscript
権利情報	This is the accepted version of the following article: Therapeutic Potential of the Prolyl Hydroxylase Inhibitor Roxadustat in a Mouse Hindlimb Lymphedema Model, Yoshitada Hoshino, Masayuki Osawa, Emi Funayama, Kosuke Ishikawa, Takahiro Miura, Masahiro Hojo, Yuhei Yamamoto, and Taku Maeda, Lymphatic Research and Biology 2023 21:4, 372-380, which has now been formally published in final form at Lymphatic Research and Biology at 10.1089/lrb.2022.0071.
PISSN	1539-6851
EISSN	1557-8585
関連情報 (isVersionOf)	出版社版DOI https://doi.org/10.1089/lrb.2022.0071