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 |
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タイトル |
Linagliptin Ameliorates Methylglyoxal-Induced Peritoneal Fibrosis in Mice |
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言語 |
en |
作成者 |
Nagai, Takuo
Doi, Shigehiro
Nakashima, Ayumu
Irifuku, Taisuke
Sasaki, Kensuke
Ueno, Toshinori
Masaki, Takao
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アクセス権 |
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アクセス権 |
open access |
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アクセス権URI |
http://purl.org/coar/access_right/c_abf2 |
権利情報 |
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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 |
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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. |
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言語 |
en |
内容記述 |
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内容記述タイプ |
Other |
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内容記述 |
This work was supported by a grant from Ryokufukai and the Japanese Association of Dialysis Physicians. |
出版者 |
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出版者 |
Public Library of Science |
言語 |
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言語 |
eng |
資源タイプ |
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資源タイプ識別子 |
http://purl.org/coar/resource_type/c_6501 |
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資源タイプ |
journal article |
出版タイプ |
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出版タイプ |
VoR |
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出版タイプResource |
http://purl.org/coar/version/c_970fb48d4fbd8a85 |
関連情報 |
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識別子タイプ |
DOI |
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関連識別子 |
10.1371/journal.pone.0160993 |
関連情報 |
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識別子タイプ |
DOI |
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関連識別子 |
https://doi.org/10.1371/journal.pone.0160993 |
収録物識別子 |
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収録物識別子タイプ |
ISSN |
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収録物識別子 |
1932-6203 |
開始ページ |
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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
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旧ID |
47658 |