Decreased ferroportin in hepatocytes promotes macrophages polarize towards an M2-like phenotype and liver fibrosis

Abstract Iron release from macrophages is closely regulated by the interaction of hepcidin, a peptide hormone produced by hepatocytes, with the macrophage iron exporter ferroportin (FPN1). However, the functions of FPN1 in hepatocyte secretion and macrophage polarization remain unknown. CD68 immunoh...

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Autores principales:	Chengyuan Cai, Danning Zeng, Qing Gao, Lei Ma, Bohang Zeng, Yi Zhou, He Wang
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/77412676414c410fb985a80a42031727
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spelling	oai:doaj.org-article:77412676414c410fb985a80a420317272021-12-02T16:31:54ZDecreased ferroportin in hepatocytes promotes macrophages polarize towards an M2-like phenotype and liver fibrosis10.1038/s41598-021-92839-z2045-2322https://doaj.org/article/77412676414c410fb985a80a420317272021-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-92839-zhttps://doaj.org/toc/2045-2322Abstract Iron release from macrophages is closely regulated by the interaction of hepcidin, a peptide hormone produced by hepatocytes, with the macrophage iron exporter ferroportin (FPN1). However, the functions of FPN1 in hepatocyte secretion and macrophage polarization remain unknown. CD68 immunohistochemical staining and double immunofluorescence staining for F4/80 and Ki67 in transgenic mouse livers showed that the number of macrophages in FPN1 −/+ and FPN1 −/− mouse livers was significantly increased compared to that in WT (FPN +/+) mice. FPN1 downregulation in hepatic cells increased the levels of the M2 markers CD206, TGF- β, VEGF, MMP-9, Laminin, Collagen, IL-4 and IL-10. Furthermore, the expression of CD16/32 and iNOS, as M1 markers, exhibited the opposite trend. Meanwhile, α-SMA immunohistochemistry and Sirius red staining showed that the trend of liver fibrosis in FPN1 −/− mice was more significant than that in control mice. Similarly, in vitro FPN1 knockdown in L02-Sh/L02-SCR liver cell lines yielded similar results. Taken together, we demonstrated that downregulated FPN1 expression in hepatocytes can promote the proliferation and polarization of macrophages, leading to hepatic fibrosis. Above all, the FPN1 axis might provide a potential target for hepatic fibrosis.Chengyuan CaiDanning ZengQing GaoLei MaBohang ZengYi ZhouHe WangNature 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 Chengyuan Cai Danning Zeng Qing Gao Lei Ma Bohang Zeng Yi Zhou He Wang Decreased ferroportin in hepatocytes promotes macrophages polarize towards an M2-like phenotype and liver fibrosis
description	Abstract Iron release from macrophages is closely regulated by the interaction of hepcidin, a peptide hormone produced by hepatocytes, with the macrophage iron exporter ferroportin (FPN1). However, the functions of FPN1 in hepatocyte secretion and macrophage polarization remain unknown. CD68 immunohistochemical staining and double immunofluorescence staining for F4/80 and Ki67 in transgenic mouse livers showed that the number of macrophages in FPN1 −/+ and FPN1 −/− mouse livers was significantly increased compared to that in WT (FPN +/+) mice. FPN1 downregulation in hepatic cells increased the levels of the M2 markers CD206, TGF- β, VEGF, MMP-9, Laminin, Collagen, IL-4 and IL-10. Furthermore, the expression of CD16/32 and iNOS, as M1 markers, exhibited the opposite trend. Meanwhile, α-SMA immunohistochemistry and Sirius red staining showed that the trend of liver fibrosis in FPN1 −/− mice was more significant than that in control mice. Similarly, in vitro FPN1 knockdown in L02-Sh/L02-SCR liver cell lines yielded similar results. Taken together, we demonstrated that downregulated FPN1 expression in hepatocytes can promote the proliferation and polarization of macrophages, leading to hepatic fibrosis. Above all, the FPN1 axis might provide a potential target for hepatic fibrosis.
format	article
author	Chengyuan Cai Danning Zeng Qing Gao Lei Ma Bohang Zeng Yi Zhou He Wang
author_facet	Chengyuan Cai Danning Zeng Qing Gao Lei Ma Bohang Zeng Yi Zhou He Wang
author_sort	Chengyuan Cai
title	Decreased ferroportin in hepatocytes promotes macrophages polarize towards an M2-like phenotype and liver fibrosis
title_short	Decreased ferroportin in hepatocytes promotes macrophages polarize towards an M2-like phenotype and liver fibrosis
title_full	Decreased ferroportin in hepatocytes promotes macrophages polarize towards an M2-like phenotype and liver fibrosis
title_fullStr	Decreased ferroportin in hepatocytes promotes macrophages polarize towards an M2-like phenotype and liver fibrosis
title_full_unstemmed	Decreased ferroportin in hepatocytes promotes macrophages polarize towards an M2-like phenotype and liver fibrosis
title_sort	decreased ferroportin in hepatocytes promotes macrophages polarize towards an m2-like phenotype and liver fibrosis
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/77412676414c410fb985a80a42031727
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Decreased ferroportin in hepatocytes promotes macrophages polarize towards an M2-like phenotype and liver fibrosis

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