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Hokkaido University Collection of Scholarly and Academic Papers >
Graduate School of Medicine / Faculty of Medicine >
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Therapeutic Potential of the Prolyl Hydroxylase Inhibitor Roxadustat in a Mouse Hindlimb Lymphedema Model
| Title: | Therapeutic Potential of the Prolyl Hydroxylase Inhibitor Roxadustat in a Mouse Hindlimb Lymphedema Model |
| Authors: | Hoshino, Yoshitada Browse this author | | Osawa, Masayuki Browse this author →KAKEN DB | | Funayama, Emi Browse this author →KAKEN DB | | Ishikawa, Kosuke Browse this author →KAKEN DB | | Miura, Takahiro Browse this author | | Hojo, Masahiro Browse this author | | Yamamoto, Yuhei Browse this author →KAKEN DB | | Maeda, Taku Browse this author |
| Keywords: | lymphedema | | roxadustat | | FG-4592 |
| Issue Date: | 1-Aug-2023 |
| Journal Title: | Lymphatic Research and Biology |
| Volume: | 21 |
| Issue: | 4 |
| Start Page: | 372 |
| End Page: | 380 |
| Publisher DOI: | 10.1089/lrb.2022.0071 |
| Abstract: | 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. |
| Rights: | 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. |
| Type: | article (author version) |
| URI: | http://hdl.handle.net/2115/88778 |
| Appears in Collections: | 医学院・医学研究院 (Graduate School of Medicine / Faculty of Medicine) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)
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Submitter: 星野 善允
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