C/EBP Homologous Protein (CHOP) Activates Macrophages and Promotes Liver Fibrosis in Schistosoma japonicum-Infected Mice

CCAAT/enhancer-binding homologous protein (CHOP), a transcriptional regulator induced by endoplasmic reticulum stress (ER stress) is a pivotal factor in the ER stress-mediated apoptosis pathway. Previous studies have shown that CHOP is involved in the formation of fibrosis in a variety of tissues an...

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Main Authors: Mengyun Duan, Yuan Yang, Shuang Peng, Xiaoqin Liu, Jixin Zhong, Yurong Guo, Min Lu, Hao Nie, Boxu Ren, Xiangzhi Zhang, Lian Liu
Format: Article
Language:English
Published: Wiley 2019-01-01
Series:Journal of Immunology Research
Online Access:http://dx.doi.org/10.1155/2019/5148575
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author Mengyun Duan
Yuan Yang
Shuang Peng
Xiaoqin Liu
Jixin Zhong
Yurong Guo
Min Lu
Hao Nie
Boxu Ren
Xiangzhi Zhang
Lian Liu
author_facet Mengyun Duan
Yuan Yang
Shuang Peng
Xiaoqin Liu
Jixin Zhong
Yurong Guo
Min Lu
Hao Nie
Boxu Ren
Xiangzhi Zhang
Lian Liu
author_sort Mengyun Duan
collection DOAJ
description CCAAT/enhancer-binding homologous protein (CHOP), a transcriptional regulator induced by endoplasmic reticulum stress (ER stress) is a pivotal factor in the ER stress-mediated apoptosis pathway. Previous studies have shown that CHOP is involved in the formation of fibrosis in a variety of tissues and is associated with alternative macrophage activation. The role of CHOP in the pathologic effects of liver fibrosis in schistosomiasis has not been reported, and underlying mechanisms remain unclear. This study is aimed at understanding the effect of CHOP on liver fibrosis induced by Schistosoma japonicum (S. japonicum) in vivo and clarifying its mechanism. C57BL/6 mice were infected with cercariae of S. japonicum through the abdominal skin. The liver fibrosis was examined. The level of IL-13 was observed. The expressions of CHOP, Krüppel-like factor 4 (KLF4), signal transducer and activator of transcription 6 (STAT6), phosphorylation STAT6, interleukin-13 receptor alpha 1 (IL-13Rα1), and interleukin-4 receptor alpha (IL-4Rα) were analysed. The eosinophilic granuloma and collagen deposition were found around the eggs in mice infected for 6 and 10 weeks. IL-13 in plasma and IL-13Rα1 and IL-4Rα in liver tissue were significantly increased. The phosphorylated STAT6 was enhanced while Krüppel-like factor 4 (KLF4) was decreased in liver tissue. The expression of CHOP and colocalization of CHOP and CD206 were increased. Overall, these results suggest that CHOP plays a critical role in hepatic fibrosis induced by S. japonicum, likely through promoting alternative activation of macrophages.
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spelling doaj-art-bea5f81ff9f642aeb4a530a31bdbbb202025-08-20T02:18:35ZengWileyJournal of Immunology Research2314-88612314-71562019-01-01201910.1155/2019/51485755148575C/EBP Homologous Protein (CHOP) Activates Macrophages and Promotes Liver Fibrosis in Schistosoma japonicum-Infected MiceMengyun Duan0Yuan Yang1Shuang Peng2Xiaoqin Liu3Jixin Zhong4Yurong Guo5Min Lu6Hao Nie7Boxu Ren8Xiangzhi Zhang9Lian Liu10Department of Medical Imaging, Medical School of Yangtze University, Jingzhou 434023, ChinaDepartment of Radiology, Renmin Hospital of Wuhan University, Wuhan 430060, ChinaDepartment of Medical Imaging, Medical School of Yangtze University, Jingzhou 434023, ChinaDepartment of Medical Imaging, Medical School of Yangtze University, Jingzhou 434023, ChinaCardiovascular Research Institute, Case Western Reserve University, Cleveland, OH 44106, USADepartment of Medical Imaging, Medical School of Yangtze University, Jingzhou 434023, ChinaDepartment of Medical Imaging, Medical School of Yangtze University, Jingzhou 434023, ChinaDepartment of Pathogenic Biology, Medical School of Yangtze University, Jingzhou 434023, ChinaDepartment of Medical Imaging, Medical School of Yangtze University, Jingzhou 434023, ChinaDepartment of Pharmacology, Medical School of Yangtze University, Jingzhou 434023, ChinaDepartment of Pharmacology, Medical School of Yangtze University, Jingzhou 434023, ChinaCCAAT/enhancer-binding homologous protein (CHOP), a transcriptional regulator induced by endoplasmic reticulum stress (ER stress) is a pivotal factor in the ER stress-mediated apoptosis pathway. Previous studies have shown that CHOP is involved in the formation of fibrosis in a variety of tissues and is associated with alternative macrophage activation. The role of CHOP in the pathologic effects of liver fibrosis in schistosomiasis has not been reported, and underlying mechanisms remain unclear. This study is aimed at understanding the effect of CHOP on liver fibrosis induced by Schistosoma japonicum (S. japonicum) in vivo and clarifying its mechanism. C57BL/6 mice were infected with cercariae of S. japonicum through the abdominal skin. The liver fibrosis was examined. The level of IL-13 was observed. The expressions of CHOP, Krüppel-like factor 4 (KLF4), signal transducer and activator of transcription 6 (STAT6), phosphorylation STAT6, interleukin-13 receptor alpha 1 (IL-13Rα1), and interleukin-4 receptor alpha (IL-4Rα) were analysed. The eosinophilic granuloma and collagen deposition were found around the eggs in mice infected for 6 and 10 weeks. IL-13 in plasma and IL-13Rα1 and IL-4Rα in liver tissue were significantly increased. The phosphorylated STAT6 was enhanced while Krüppel-like factor 4 (KLF4) was decreased in liver tissue. The expression of CHOP and colocalization of CHOP and CD206 were increased. Overall, these results suggest that CHOP plays a critical role in hepatic fibrosis induced by S. japonicum, likely through promoting alternative activation of macrophages.http://dx.doi.org/10.1155/2019/5148575
spellingShingle Mengyun Duan
Yuan Yang
Shuang Peng
Xiaoqin Liu
Jixin Zhong
Yurong Guo
Min Lu
Hao Nie
Boxu Ren
Xiangzhi Zhang
Lian Liu
C/EBP Homologous Protein (CHOP) Activates Macrophages and Promotes Liver Fibrosis in Schistosoma japonicum-Infected Mice
Journal of Immunology Research
title C/EBP Homologous Protein (CHOP) Activates Macrophages and Promotes Liver Fibrosis in Schistosoma japonicum-Infected Mice
title_full C/EBP Homologous Protein (CHOP) Activates Macrophages and Promotes Liver Fibrosis in Schistosoma japonicum-Infected Mice
title_fullStr C/EBP Homologous Protein (CHOP) Activates Macrophages and Promotes Liver Fibrosis in Schistosoma japonicum-Infected Mice
title_full_unstemmed C/EBP Homologous Protein (CHOP) Activates Macrophages and Promotes Liver Fibrosis in Schistosoma japonicum-Infected Mice
title_short C/EBP Homologous Protein (CHOP) Activates Macrophages and Promotes Liver Fibrosis in Schistosoma japonicum-Infected Mice
title_sort c ebp homologous protein chop activates macrophages and promotes liver fibrosis in schistosoma japonicum infected mice
url http://dx.doi.org/10.1155/2019/5148575
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