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Linagliptin Ameliorates Methylglyoxal-Induced Peritoneal Fibrosis in Mice

https://hiroshima.repo.nii.ac.jp/records/2007963
https://hiroshima.repo.nii.ac.jp/records/2007963
857cfaa6-08a3-462d-bdf3-10a0813b48ce
名前 / ファイル ライセンス アクション
PLoSONE_11_e0160993.pdf PLoSONE_11_e0160993.pdf (5.9 MB)
Item type デフォルトアイテムタイプ_(フル)(1)
公開日 2023-03-18
タイトル
タイトル Linagliptin Ameliorates Methylglyoxal-Induced Peritoneal Fibrosis in Mice
言語 en
作成者 Nagai, Takuo

× Nagai, Takuo

en Nagai, Takuo

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Doi, Shigehiro

× Doi, Shigehiro

en Doi, Shigehiro

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Nakashima, Ayumu

× Nakashima, Ayumu

en Nakashima, Ayumu

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Irifuku, Taisuke

× Irifuku, Taisuke

en Irifuku, Taisuke

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Sasaki, Kensuke

× Sasaki, Kensuke

en Sasaki, Kensuke

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Ueno, Toshinori

× Ueno, Toshinori

en Ueno, Toshinori

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Masaki, Takao

× Masaki, Takao

en Masaki, Takao

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アクセス権
アクセス権 open access
アクセス権URI http://purl.org/coar/access_right/c_abf2
権利情報
権利情報 © 2016 Nagai et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
内容記述
内容記述 Recent studies have reported increases of methylglyoxal (MGO) in peritoneal dialysis patients, and that MGO-mediated inflammation plays an important role in the development of peritoneal fibrosis through production of transforming growth factor-β1 (TGF-β1). Linagliptin, a dipeptidyl peptidase-4 inhibitor, exerts anti-inflammatory effects independent of blood glucose levels. In this study, we examined whether linagliptin suppresses MGOinduced peritoneal fibrosis in mice. Male C57/BL6 mice were divided into three groups: control, MGO injection plus saline, and MGO injection plus linagliptin (n = 6 per group). Peritoneal fibrosis was induced by daily intraperitoneal injection of saline containing 40 mmol/L MGO for 21 days. Saline was administered intraperitoneally to the control group. Linagliptin (10 mg/kg) or saline were administrated by once-daily oral gavage from 3 weeks before starting MGO injections. Immunohistochemical staining revealed that linagliptin suppressed expression of α-smooth muscle actin and fibroblast-specific protein-1, deposition of type I and III collagen, and macrophage (F4/80) infiltration. Peritoneal equilibration testing showed improved peritoneal functions in mice treated with linagliptin. Peritoneal injection of MGO increased plasma levels of glucagon-like peptide-1 (GLP-1) in mice, and a further increase was observed in linagliptin-treated mice. Although MGO increased plasma glucose levels, linagliptin did not decrease plasma glucose levels. Moreover, linagliptin reduced the TGF-β1 concentration in the peritoneal fluid of MGO-treated mice. GLP-1 receptor (GLP-1R) was expressed in monocytes/macrophages and linagliptin suppressed GLP-1R expression in MGO-injected mice. These results suggest that oral administration of linagliptin ameliorates MGO-induced peritoneal fibrosis.
言語 en
内容記述
内容記述タイプ Other
内容記述 This work was supported by a grant from Ryokufukai and the Japanese Association of Dialysis Physicians.
出版者
出版者 Public Library of Science
言語
言語 eng
資源タイプ
資源タイプ識別子 http://purl.org/coar/resource_type/c_6501
資源タイプ journal article
出版タイプ
出版タイプ VoR
出版タイプResource http://purl.org/coar/version/c_970fb48d4fbd8a85
関連情報
識別子タイプ DOI
関連識別子 10.1371/journal.pone.0160993
関連情報
識別子タイプ DOI
関連識別子 https://doi.org/10.1371/journal.pone.0160993
収録物識別子
収録物識別子タイプ ISSN
収録物識別子 1932-6203
開始ページ
開始ページ e0160993
書誌情報 PLoS ONE
PLoS ONE

巻 11, 号 8, p. e0160993, 発行日 2016-08-11
旧ID 47658
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