A synthetic retinoic acid receptor agonist Am80 ameliorates renal fibrosis via inducing the production of alpha-1-acid glycoprotein

Abstract Renal fibrosis is a major factor in the progression of chronic kidney disease and the final common pathway of kidney injury. Therefore, the effective therapies against renal fibrosis are urgently needed. The objective of this study was to investigate the effect of Am80, a synthetic retinoic...

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Autores principales:	Hiroshi Watanabe, Jing Bi, Ryota Murata, Rui Fujimura, Kento Nishida, Tadashi Imafuku, Yuka Nakamura, Hitoshi Maeda, Ayumi Mukunoki, Toru Takeo, Naomi Nakagata, Yuki Kurauchi, Hiroshi Katsuki, Motoko Tanaka, Kazutaka Matsushita, Masafumi Fukagawa, Toru Maruyama
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2020
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/e6a55831e6dd47b6b8c66052bc944aec
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spelling	oai:doaj.org-article:e6a55831e6dd47b6b8c66052bc944aec2021-12-02T16:24:49ZA synthetic retinoic acid receptor agonist Am80 ameliorates renal fibrosis via inducing the production of alpha-1-acid glycoprotein10.1038/s41598-020-68337-z2045-2322https://doaj.org/article/e6a55831e6dd47b6b8c66052bc944aec2020-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-020-68337-zhttps://doaj.org/toc/2045-2322Abstract Renal fibrosis is a major factor in the progression of chronic kidney disease and the final common pathway of kidney injury. Therefore, the effective therapies against renal fibrosis are urgently needed. The objective of this study was to investigate the effect of Am80, a synthetic retinoic acid receptor (RAR) agonist, in the treatment of renal interstitial fibrosis using unilateral ureteral obstruction (UUO) mice. The findings indicate that Am80 treatment suppressed renal fibrosis and inflammation to the same degree as the naturally-occuring retinoic acid, all-trans retinoic acid (atRA). But the adverse effect of body weight loss in Am80-treated mice was lower compared to the atRA treatment. The hepatic mRNA levels of alpha-1-acid glycoprotein (AGP), a downstream molecule of RAR agonist, was increased following administration of Am80 to healthy mice. In addition, increased AGP mRNA expression was also observed in HepG2 cells and THP-1-derived macrophages that had been treated with Am80. AGP-knockout mice exacerbated renal fibrosis, inflammation and macrophage infiltration in UUO mice, indicating endogenous AGP played an anti-fibrotic and anti-inflammatory role during the development of renal fibrosis. We also found that no anti-fibrotic effect of Am80 was observed in UUO-treated AGP-knockout mice whereas atRA treatment tended to show a partial anti-fibrotic effect. These collective findings suggest that Am80 protects against renal fibrosis via being involved in AGP function.Hiroshi WatanabeJing BiRyota MurataRui FujimuraKento NishidaTadashi ImafukuYuka NakamuraHitoshi MaedaAyumi MukunokiToru TakeoNaomi NakagataYuki KurauchiHiroshi KatsukiMotoko TanakaKazutaka MatsushitaMasafumi FukagawaToru MaruyamaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 10, Iss 1, Pp 1-9 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Hiroshi Watanabe Jing Bi Ryota Murata Rui Fujimura Kento Nishida Tadashi Imafuku Yuka Nakamura Hitoshi Maeda Ayumi Mukunoki Toru Takeo Naomi Nakagata Yuki Kurauchi Hiroshi Katsuki Motoko Tanaka Kazutaka Matsushita Masafumi Fukagawa Toru Maruyama A synthetic retinoic acid receptor agonist Am80 ameliorates renal fibrosis via inducing the production of alpha-1-acid glycoprotein
description	Abstract Renal fibrosis is a major factor in the progression of chronic kidney disease and the final common pathway of kidney injury. Therefore, the effective therapies against renal fibrosis are urgently needed. The objective of this study was to investigate the effect of Am80, a synthetic retinoic acid receptor (RAR) agonist, in the treatment of renal interstitial fibrosis using unilateral ureteral obstruction (UUO) mice. The findings indicate that Am80 treatment suppressed renal fibrosis and inflammation to the same degree as the naturally-occuring retinoic acid, all-trans retinoic acid (atRA). But the adverse effect of body weight loss in Am80-treated mice was lower compared to the atRA treatment. The hepatic mRNA levels of alpha-1-acid glycoprotein (AGP), a downstream molecule of RAR agonist, was increased following administration of Am80 to healthy mice. In addition, increased AGP mRNA expression was also observed in HepG2 cells and THP-1-derived macrophages that had been treated with Am80. AGP-knockout mice exacerbated renal fibrosis, inflammation and macrophage infiltration in UUO mice, indicating endogenous AGP played an anti-fibrotic and anti-inflammatory role during the development of renal fibrosis. We also found that no anti-fibrotic effect of Am80 was observed in UUO-treated AGP-knockout mice whereas atRA treatment tended to show a partial anti-fibrotic effect. These collective findings suggest that Am80 protects against renal fibrosis via being involved in AGP function.
format	article
author	Hiroshi Watanabe Jing Bi Ryota Murata Rui Fujimura Kento Nishida Tadashi Imafuku Yuka Nakamura Hitoshi Maeda Ayumi Mukunoki Toru Takeo Naomi Nakagata Yuki Kurauchi Hiroshi Katsuki Motoko Tanaka Kazutaka Matsushita Masafumi Fukagawa Toru Maruyama
author_facet	Hiroshi Watanabe Jing Bi Ryota Murata Rui Fujimura Kento Nishida Tadashi Imafuku Yuka Nakamura Hitoshi Maeda Ayumi Mukunoki Toru Takeo Naomi Nakagata Yuki Kurauchi Hiroshi Katsuki Motoko Tanaka Kazutaka Matsushita Masafumi Fukagawa Toru Maruyama
author_sort	Hiroshi Watanabe
title	A synthetic retinoic acid receptor agonist Am80 ameliorates renal fibrosis via inducing the production of alpha-1-acid glycoprotein
title_short	A synthetic retinoic acid receptor agonist Am80 ameliorates renal fibrosis via inducing the production of alpha-1-acid glycoprotein
title_full	A synthetic retinoic acid receptor agonist Am80 ameliorates renal fibrosis via inducing the production of alpha-1-acid glycoprotein
title_fullStr	A synthetic retinoic acid receptor agonist Am80 ameliorates renal fibrosis via inducing the production of alpha-1-acid glycoprotein
title_full_unstemmed	A synthetic retinoic acid receptor agonist Am80 ameliorates renal fibrosis via inducing the production of alpha-1-acid glycoprotein
title_sort	synthetic retinoic acid receptor agonist am80 ameliorates renal fibrosis via inducing the production of alpha-1-acid glycoprotein
publisher	Nature Portfolio
publishDate	2020
url	https://doaj.org/article/e6a55831e6dd47b6b8c66052bc944aec
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A synthetic retinoic acid receptor agonist Am80 ameliorates renal fibrosis via inducing the production of alpha-1-acid glycoprotein

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