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Pivotal roles of Kupffer cells in the progression and regression of DDC-induced chronic cholangiopathy

Kupffer cells (KCs) are key players in maintaining tissue homeostasis and are involved in various liver diseases. However, the roles of KCs in the pathogenesis of cholangiopathy are largely unknown. We aimed to investigate the precise roles of KCs in both the progression and regression phases of the...

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Autores principales: Jemail, Leila, Miyao, Masashi, Kotani, Hirokazu, Kawai, Chihiro, Minami, Hirozo, Abiru, Hitoshi, Tamaki, Keiji
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5913224/
https://www.ncbi.nlm.nih.gov/pubmed/29686325
http://dx.doi.org/10.1038/s41598-018-24825-x
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author Jemail, Leila
Miyao, Masashi
Kotani, Hirokazu
Kawai, Chihiro
Minami, Hirozo
Abiru, Hitoshi
Tamaki, Keiji
author_facet Jemail, Leila
Miyao, Masashi
Kotani, Hirokazu
Kawai, Chihiro
Minami, Hirozo
Abiru, Hitoshi
Tamaki, Keiji
author_sort Jemail, Leila
collection PubMed
description Kupffer cells (KCs) are key players in maintaining tissue homeostasis and are involved in various liver diseases. However, the roles of KCs in the pathogenesis of cholangiopathy are largely unknown. We aimed to investigate the precise roles of KCs in both the progression and regression phases of the 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC)-induced cholangiopathy model. In the early phase of DDC-induced cholangiopathy, the number of KCs significantly increased over time. Moreover, KCs were associated with abnormal phenotypic changes in other liver cells, such as hepatocytes, biliary epithelial cells, liver sinusoidal endothelial cells, and hepatic stellate cells. In contrast, KC depletion by clodronate administration suppressed the progression of the disease, and maintained the phenotypes of other cells. In the regression phase, the numbers of KCs significantly decreased, and the cells redifferentiated to their quiescent state. In contrast, KC depletion delayed the recovery of cells by maintaining other liver cells in an active state. These findings suggest that KCs play detrimental roles in the progression phase; however, they are beneficial in the regression phase by mediating interactions between other liver cells. Our data provide new insights into the roles of KCs in the pathogenesis of cholangiopathy.
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spelling pubmed-59132242018-04-30 Pivotal roles of Kupffer cells in the progression and regression of DDC-induced chronic cholangiopathy Jemail, Leila Miyao, Masashi Kotani, Hirokazu Kawai, Chihiro Minami, Hirozo Abiru, Hitoshi Tamaki, Keiji Sci Rep Article Kupffer cells (KCs) are key players in maintaining tissue homeostasis and are involved in various liver diseases. However, the roles of KCs in the pathogenesis of cholangiopathy are largely unknown. We aimed to investigate the precise roles of KCs in both the progression and regression phases of the 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC)-induced cholangiopathy model. In the early phase of DDC-induced cholangiopathy, the number of KCs significantly increased over time. Moreover, KCs were associated with abnormal phenotypic changes in other liver cells, such as hepatocytes, biliary epithelial cells, liver sinusoidal endothelial cells, and hepatic stellate cells. In contrast, KC depletion by clodronate administration suppressed the progression of the disease, and maintained the phenotypes of other cells. In the regression phase, the numbers of KCs significantly decreased, and the cells redifferentiated to their quiescent state. In contrast, KC depletion delayed the recovery of cells by maintaining other liver cells in an active state. These findings suggest that KCs play detrimental roles in the progression phase; however, they are beneficial in the regression phase by mediating interactions between other liver cells. Our data provide new insights into the roles of KCs in the pathogenesis of cholangiopathy. Nature Publishing Group UK 2018-04-23 /pmc/articles/PMC5913224/ /pubmed/29686325 http://dx.doi.org/10.1038/s41598-018-24825-x Text en © The Author(s) 2018 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Jemail, Leila
Miyao, Masashi
Kotani, Hirokazu
Kawai, Chihiro
Minami, Hirozo
Abiru, Hitoshi
Tamaki, Keiji
Pivotal roles of Kupffer cells in the progression and regression of DDC-induced chronic cholangiopathy
title Pivotal roles of Kupffer cells in the progression and regression of DDC-induced chronic cholangiopathy
title_full Pivotal roles of Kupffer cells in the progression and regression of DDC-induced chronic cholangiopathy
title_fullStr Pivotal roles of Kupffer cells in the progression and regression of DDC-induced chronic cholangiopathy
title_full_unstemmed Pivotal roles of Kupffer cells in the progression and regression of DDC-induced chronic cholangiopathy
title_short Pivotal roles of Kupffer cells in the progression and regression of DDC-induced chronic cholangiopathy
title_sort pivotal roles of kupffer cells in the progression and regression of ddc-induced chronic cholangiopathy
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5913224/
https://www.ncbi.nlm.nih.gov/pubmed/29686325
http://dx.doi.org/10.1038/s41598-018-24825-x
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