Xiaochaihu decorction relieves liver fibrosis caused by  Schistosoma japonicum  infection  via  the HSP47/TGF-β pathway

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Abstract

Background

Hepatic fibrosis caused by chronic infection with Schistosoma japonica remains a serious public health problem in the world. Symptoms include inflammation, liver granuloma and fibrosis, whilst treatment options are still limited. This study aims to investigate whether and how traditional Chinese medicine Xiaochaihu decoction (XCH) could mitigate liver fibrosis caused by S. japonicum infection.

Methods

BALB/c mice were infected with S. japonicum cercariae and treated with XCH for 16 weeks. Liver pathological changes were assessed by H&E and Masson staining. NIH3T3 and Raw264.7 cells were treated with S. japonicum egg antigens with or without XCH treatment. Quantitative real-time PCR, western blot, immunfluorescence and ELISA were performed to determine the changes of levels of fibrogenic markers.

Results

XCH protected mouse liver from injuries and fibrosis caused by S. japonicum infection and considerably reduced egg burden in a dose-dependent manner. Infection with S. japonicum caused elevation of serum ALT, AST, ALP, HA and PIIINP levels and reduction of ALB and GLOB levels, which was markedly suppressed by XCH. The upregulation of TGF-β1, Hsp47, α-SMA, Col1A1 and Col3A1 in S. japonicum-infected mouse liver was also significantly inhibited by XCH. Schistosoma japonicum egg antigens promoted the expression of Hsp47, TGF-β1, Timp-1, α-SMA, Col1A1 and Col3A1 in NIH3T3 cells, and TGF-β1, CTGF, IL-13, IL-17 and IL-6 in Raw264.7 cells, which was inhibited by XCH, LY2157299 and shRNA-Hsp47.

Conclusions

These results demonstrated that the hepatic protective effects of Xiaochaihu decoction were mediated by HSP47/TGF-β axis.

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Most cited references 33

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Schistosomiasis

Donald McManus, David Dunne, Moussa Sacko … (2018)

Schistosomiasis (bilharzia) is a neglected tropical disease caused by parasitic flatworms (blood flukes) of the genus Schistosoma, with considerable morbidity in parts of the Middle East, South America, Southeast Asia and, particularly, in sub-Saharan Africa. Infective larvae grow in an intermediate host (fresh-water snails) before penetrating the skin of the definitive human host. Mature adult worms reside in the mesenteric (Schistosoma mansoni and Schistosoma japonicum) or pelvic (Schistosoma haematobium) veins, where female worms lay eggs, which are secreted in stool or urine. Eggs trapped in the surrounding tissues and organs, such as the liver and bladder, cause inflammatory immune responses (including granulomas) that result in intestinal, hepato-splenic or urogenital disease. Diagnosis requires the detection of eggs in excreta or worm antigens in the serum, and sensitive, rapid, point-of-care tests for populations living in endemic areas are needed. The anti-schistosomal drug praziquantel is safe and efficacious against adult worms of all the six Schistosoma spp. infecting humans; however, it does not prevent reinfection and the emergence of drug resistance is a concern. Schistosomiasis elimination will require a multifaceted approach, including: treatment; snail control; information, education and communication; improved water, sanitation and hygiene; accurate diagnostics; and surveillance-response systems that are readily tailored to social-ecological settings.

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Effect of modulation of PPAR-γ activity on Kupffer cells M1/M2 polarization in the development of non-alcoholic fatty liver disease

Wenjing Luo, Qinyu Xu, Qi Wang … (2017)

Abnormal lipid-mediated hepatic inflammatory-immune dysfunction and chronic low grade inflammation play an important role in the pathogenesis of non-alcoholic fatty liver disease (NAFLD). Macrophage polarization is an important mechanism for the regulation of inflammatory response. Since PPAR-γ has emerged as a master regulator of macrophage polarization, we aimed to investigate the lipid-induced macrophage/Kupffer cell polarization in vivo and in vitro, and explore the association between PPAR-γ activity and macrophages M1/M2 polarization shifting. Here we showed that long-term high-fat diet increased Kupffer cells content with M1-predominant phenotype and increasing production of pro-inflammatory cytokines. Saturated fatty acids polarized Kupffer cells/macrophages to an M1-predominant phenotype while n-3 PUFA polarized Kupffer cells/macrophages to an M2 phenotype, which was associated with activation of NF-κB signal pathway and PPAR-γ respectively. Furthermore, up-regulation of PPAR-γ shifted lipid-induced macrophages polarization from M1-predominant phenotype to M2 phenotype. Macrophages polarization switch was associated with the interaction between PPAR-γ and NF-κBp65 signal pathway. Rosiglitazone restored high-fat diet-induced imblance of Kupffer cells M1/M2 polarization and alleviated hepatic steatosis as well as local pro-inflammatory response. These findings suggest that manipulation of PPAR-γ activity has the potential to balance lipid-induced M1/M2 macrophage/Kupffer cell polarization, and leading to prevent the development of NAFLD.

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Biology of Hsp47 (Serpin H1), a collagen-specific molecular chaperone.

Shinya Ito, Kazuhiro Nagata (2017)

Hsp47, a collagen-specific molecular chaperone that localizes in the endoplasmic reticulum (ER), is indispensable for molecular maturation of collagen. Hsp47, which is encoded by the SERPINH1 gene, belongs to the serpin family and has the serpin fold; however, it has no serine protease inhibitory activity. Hsp47 transiently binds to procollagen in the ER, dissociates in the cis-Golgi or ER-Golgi intermediate compartment (ERGIC) in a pH-dependent manner, and is then transported back to the ER via its RDEL retention sequence. Hsp47 recognizes collagenous (Gly-Xaa-Arg) repeats on triple-helical procollagen and can prevent local unfolding and/or aggregate formation of procollagen. Gene disruption of Hsp47 in mice causes embryonic lethality due to impairments in basement membrane and collagen fibril formation. In Hsp47-knockout cells, the type I collagen triple helix forms abnormally, resulting in thin and frequently branched fibrils. Secretion of type I collagens is slow and plausible in making aggregates of procollagens in the ER of hsp47-knocked out fibroblasts, which are ultimately degraded by autophagy. Mutations in Hsp47 are causally associated with osteogenesis imperfecta. Expression of Hsp47 is strongly correlated with expression of collagens in multiple types of cells and tissues. Therefore, Hsp47 represents a promising target for treatment of collagen-related disorders, including fibrosis of the liver, lung, and other organs.

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Author and article information

Contributors

Yuzheng Huang: yzhyz01@163.com

Jin Lu: 1982277564@qq.com

Yongliang Xu: 2366449388@qq.com

Chunrong Xiong: maiya711@163.com

Deshen Tong: tds4199@163.com

Nannan Hu: 947688546@qq.com

Haitao Yang: yht@jscdc.cn

Journal

Journal ID (nlm-ta): Parasit Vectors

Journal ID (iso-abbrev): Parasit Vectors

Title: Parasites & Vectors

Publisher: BioMed Central (London )

ISSN (Electronic): 1756-3305

Publication date (Electronic): 14 May 2020

Publication date PMC-release: 14 May 2020

Publication date Collection: 2020

Volume: 13

Electronic Location Identifier: 254

Affiliations

[1 ]GRID grid.452515.2, National Health Commission Key Laboratory of Parasitic Disease Control and Prevention, Jiangsu Provincial Key Laboratory on Parasite and Vector Control Technology, , Jiangsu Institute of Parasitic Diseases, ; 117 Meiyuan Yangxiang, Wuxi, 214064 Jiangsu China

[2 ]GRID grid.258151.a, ISNI 0000 0001 0708 1323, Public Health Research Center, , Jiangnan University, ; Wuxi, 214122 Jiangsu Province China

[3 ]GRID grid.89957.3a, ISNI 0000 0000 9255 8984, Center for Global Health, School of Public Health, , Nanjing Medical University, ; Nanjing, 211166 China

Article

Publisher ID: 4121

DOI: 10.1186/s13071-020-04121-2

PMC ID: 7227055

PubMed ID: 32410640

SO-VID: 7fd5823f-f96d-403f-aa3a-2c6c699b4f78

License:

Open AccessThis 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 licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence 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 licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

History

Date received : 7 September 2019

Date accepted : 6 May 2020

Funding

Funded by: Natural Science Foundation of Jilin Province (CN)

Award ID: 81673673

Award Recipient : Yuzheng Huang

Funded by: Project of Public Health Research Center of Jiangnan University

Award ID: JUPH201811

Award Recipient : Yuzheng Huang

Funded by: the Project of Invigorating Health Care through Science, Technology and Education

Award ID: ZDXKA2016016

Award Recipient : Haitao Yang

Funded by: the Jiangsu Provincial Department of Science and Technology

Award ID: BM2018020

Award ID: BE2016631

Award ID: BM2015024

Award Recipient : Haitao Yang

Funded by: Funding of Wuxi Science and Technology development

Award ID: WX0302B010504180001PB

Award Recipient : Yuzheng Huang

Custom metadata

ScienceOpen disciplines: Parasitology

Keywords: xiaochaihu decorction,schistosoma japonicum,hepatic fibrosis,hsp47,tgf-β

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ScienceOpen disciplines: Parasitology

Keywords: xiaochaihu decorction, schistosoma japonicum, hepatic fibrosis, hsp47, tgf-β

Xiaochaihu decorction relieves liver fibrosis caused by Schistosoma japonicum infection via the HSP47/TGF-β pathway

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Abstract

Background

Methods

Results

Conclusions

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Decoding Infection and Transmission

Most cited references 33

Schistosomiasis

Effect of modulation of PPAR-γ activity on Kupffer cells M1/M2 polarization in the development of non-alcoholic fatty liver disease

Biology of Hsp47 (Serpin H1), a collagen-specific molecular chaperone.

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