Interferon-γ enhances the therapeutic effect of mesenchymal stem cells on experimental renal fibrosis

Abstract Mesenchymal stem cells (MSCs) administered for therapeutic purposes can be activated by interferon-γ (IFN-γ) secreted from natural killer cells in injured tissues and exert anti-inflammatory effects. These processes require a substantial period of time, leading to a delayed onset of MSCs’ t...

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Autores principales:	Ryo Kanai, Ayumu Nakashima, Shigehiro Doi, Tomoe Kimura, Ken Yoshida, Satoshi Maeda, Naoki Ishiuchi, Yumi Yamada, Takeshi Ike, Toshiki Doi, Yukio Kato, Takao Masaki
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/837c468c6a7d4fe9b0d5a28c99abc8c6
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spelling	oai:doaj.org-article:837c468c6a7d4fe9b0d5a28c99abc8c62021-12-02T14:01:20ZInterferon-γ enhances the therapeutic effect of mesenchymal stem cells on experimental renal fibrosis10.1038/s41598-020-79664-62045-2322https://doaj.org/article/837c468c6a7d4fe9b0d5a28c99abc8c62021-01-01T00:00:00Zhttps://doi.org/10.1038/s41598-020-79664-6https://doaj.org/toc/2045-2322Abstract Mesenchymal stem cells (MSCs) administered for therapeutic purposes can be activated by interferon-γ (IFN-γ) secreted from natural killer cells in injured tissues and exert anti-inflammatory effects. These processes require a substantial period of time, leading to a delayed onset of MSCs’ therapeutic effects. In this study, we investigated whether pretreatment with IFN-γ could potentiate the anti-fibrotic ability of MSCs in rats with ischemia–reperfusion injury (IRI) and unilateral ureter obstruction. Administration of MSCs treated with IFN-γ strongly reduced infiltration of inflammatory cells and ameliorated interstitial fibrosis compared with control MSCs without IFN-γ treatment. In addition, conditioned medium obtained from IFN-γ-treated MSCs decreased fibrotic changes in cultured cells induced by transforming growth factor-β1 more efficiently than that from control MSCs. Most notably, secretion of prostaglandin E2 from MSCs was significantly increased by treatment with IFN-γ. Increased prostaglandin E2 in conditioned medium obtained from IFN-γ-treated MSCs induced polarization of immunosuppressive CD163 and CD206-positive macrophages. In addition, knockdown of prostaglandin E synthase weakened the anti-fibrotic effects of MSCs treated with IFN-γ in IRI rats, suggesting the involvement of prostaglandin E2 in the beneficial effects of IFN-γ. Administration of MSCs treated with IFN-γ might represent a promising therapy to prevent the progression of renal fibrosis.Ryo KanaiAyumu NakashimaShigehiro DoiTomoe KimuraKen YoshidaSatoshi MaedaNaoki IshiuchiYumi YamadaTakeshi IkeToshiki DoiYukio KatoTakao MasakiNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-14 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Ryo Kanai Ayumu Nakashima Shigehiro Doi Tomoe Kimura Ken Yoshida Satoshi Maeda Naoki Ishiuchi Yumi Yamada Takeshi Ike Toshiki Doi Yukio Kato Takao Masaki Interferon-γ enhances the therapeutic effect of mesenchymal stem cells on experimental renal fibrosis
description	Abstract Mesenchymal stem cells (MSCs) administered for therapeutic purposes can be activated by interferon-γ (IFN-γ) secreted from natural killer cells in injured tissues and exert anti-inflammatory effects. These processes require a substantial period of time, leading to a delayed onset of MSCs’ therapeutic effects. In this study, we investigated whether pretreatment with IFN-γ could potentiate the anti-fibrotic ability of MSCs in rats with ischemia–reperfusion injury (IRI) and unilateral ureter obstruction. Administration of MSCs treated with IFN-γ strongly reduced infiltration of inflammatory cells and ameliorated interstitial fibrosis compared with control MSCs without IFN-γ treatment. In addition, conditioned medium obtained from IFN-γ-treated MSCs decreased fibrotic changes in cultured cells induced by transforming growth factor-β1 more efficiently than that from control MSCs. Most notably, secretion of prostaglandin E2 from MSCs was significantly increased by treatment with IFN-γ. Increased prostaglandin E2 in conditioned medium obtained from IFN-γ-treated MSCs induced polarization of immunosuppressive CD163 and CD206-positive macrophages. In addition, knockdown of prostaglandin E synthase weakened the anti-fibrotic effects of MSCs treated with IFN-γ in IRI rats, suggesting the involvement of prostaglandin E2 in the beneficial effects of IFN-γ. Administration of MSCs treated with IFN-γ might represent a promising therapy to prevent the progression of renal fibrosis.
format	article
author	Ryo Kanai Ayumu Nakashima Shigehiro Doi Tomoe Kimura Ken Yoshida Satoshi Maeda Naoki Ishiuchi Yumi Yamada Takeshi Ike Toshiki Doi Yukio Kato Takao Masaki
author_facet	Ryo Kanai Ayumu Nakashima Shigehiro Doi Tomoe Kimura Ken Yoshida Satoshi Maeda Naoki Ishiuchi Yumi Yamada Takeshi Ike Toshiki Doi Yukio Kato Takao Masaki
author_sort	Ryo Kanai
title	Interferon-γ enhances the therapeutic effect of mesenchymal stem cells on experimental renal fibrosis
title_short	Interferon-γ enhances the therapeutic effect of mesenchymal stem cells on experimental renal fibrosis
title_full	Interferon-γ enhances the therapeutic effect of mesenchymal stem cells on experimental renal fibrosis
title_fullStr	Interferon-γ enhances the therapeutic effect of mesenchymal stem cells on experimental renal fibrosis
title_full_unstemmed	Interferon-γ enhances the therapeutic effect of mesenchymal stem cells on experimental renal fibrosis
title_sort	interferon-γ enhances the therapeutic effect of mesenchymal stem cells on experimental renal fibrosis
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/837c468c6a7d4fe9b0d5a28c99abc8c6
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Interferon-γ enhances the therapeutic effect of mesenchymal stem cells on experimental renal fibrosis

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