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Increased Expression of S100B and RAGE in a Mouse Model of Bile Duct Ligation-induced Liver Fibrosis

BACKGROUND: Liver fibrosis is defined as the accumulation of the extracellular matrix and scar formation. The receptor for advanced glycation end products (RAGE) has been demonstrated to participate in fibrogenesis. S100B is a ligand of RAGE and exerts extracellular functions by inducing a series of...

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Autores principales: Park, Ji-Won, Kim, Mo-Jong, Kim, Sung-Eun, Kim, Hee-Jun, Jeon, Yong-Chul, Shin, Hae-Young, Park, Se Jin, Jang, Myoung-Kuk, Kim, Dong-Joon, Park, Choong-Kee, Choi, Eun-Kyoung
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Korean Academy of Medical Sciences 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8042478/
https://www.ncbi.nlm.nih.gov/pubmed/33847081
http://dx.doi.org/10.3346/jkms.2021.36.e90
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author Park, Ji-Won
Kim, Mo-Jong
Kim, Sung-Eun
Kim, Hee-Jun
Jeon, Yong-Chul
Shin, Hae-Young
Park, Se Jin
Jang, Myoung-Kuk
Kim, Dong-Joon
Park, Choong-Kee
Choi, Eun-Kyoung
author_facet Park, Ji-Won
Kim, Mo-Jong
Kim, Sung-Eun
Kim, Hee-Jun
Jeon, Yong-Chul
Shin, Hae-Young
Park, Se Jin
Jang, Myoung-Kuk
Kim, Dong-Joon
Park, Choong-Kee
Choi, Eun-Kyoung
author_sort Park, Ji-Won
collection PubMed
description BACKGROUND: Liver fibrosis is defined as the accumulation of the extracellular matrix and scar formation. The receptor for advanced glycation end products (RAGE) has been demonstrated to participate in fibrogenesis. S100B is a ligand of RAGE and exerts extracellular functions by inducing a series of signal transduction cascades. However, the involvement of S100B and RAGE in cholestasis-induced liver fibrosis remains unclear. In this study, we investigated S100B and RAGE expression during liver fibrosis in mice that underwent common bile duct ligation (BDL). METHODS: BDL was performed in 10-week-old male C57BL/6J mice with sham control (n = 26) and BDL (n = 26) groups. Expression levels of S100B, RAGE and fibrotic markers in the livers from both groups at week 1 and 3 after BDL were examined by western blot and quantitative real-time reverse transcription polymerase chain reaction analysis. Liver fibrotic changes were examined by histological and ultrastructural analysis. RESULTS: Histological staining with Sirius Red and the evaluation of the messenger RNA expression of fibrotic markers showed noticeable periportal fibrosis and bile duct proliferation. S100B was mainly present in bile duct epithelial cells, and its expression was upregulated in proportion to the ductular reaction during fibrogenesis by BDL. RAGE expression was also increased, and interestingly, triple immunofluorescence staining and transmission electron microscopy showed that both S100B and RAGE were expressed in proliferating bile duct epithelial cells and activated hepatic stellate cells (HSCs) of the BDL livers. In addition, in rat HSCs (HSC-T6), treatment with recombinant S100B protein significantly increased fibrotic markers in a dose-dependent manner, and RAGE small interfering RNA (siRNA) suppressed S100B-stimulated upregulation of fibrotic markers compared with cells treated with scramble siRNA and S100B. CONCLUSION: These findings suggest that the increased expression of S100B and RAGE and the interaction between S100B and RAGE may play an important role in ductular reaction and liver fibrosis induced by BDL.
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spelling pubmed-80424782021-04-20 Increased Expression of S100B and RAGE in a Mouse Model of Bile Duct Ligation-induced Liver Fibrosis Park, Ji-Won Kim, Mo-Jong Kim, Sung-Eun Kim, Hee-Jun Jeon, Yong-Chul Shin, Hae-Young Park, Se Jin Jang, Myoung-Kuk Kim, Dong-Joon Park, Choong-Kee Choi, Eun-Kyoung J Korean Med Sci Original Article BACKGROUND: Liver fibrosis is defined as the accumulation of the extracellular matrix and scar formation. The receptor for advanced glycation end products (RAGE) has been demonstrated to participate in fibrogenesis. S100B is a ligand of RAGE and exerts extracellular functions by inducing a series of signal transduction cascades. However, the involvement of S100B and RAGE in cholestasis-induced liver fibrosis remains unclear. In this study, we investigated S100B and RAGE expression during liver fibrosis in mice that underwent common bile duct ligation (BDL). METHODS: BDL was performed in 10-week-old male C57BL/6J mice with sham control (n = 26) and BDL (n = 26) groups. Expression levels of S100B, RAGE and fibrotic markers in the livers from both groups at week 1 and 3 after BDL were examined by western blot and quantitative real-time reverse transcription polymerase chain reaction analysis. Liver fibrotic changes were examined by histological and ultrastructural analysis. RESULTS: Histological staining with Sirius Red and the evaluation of the messenger RNA expression of fibrotic markers showed noticeable periportal fibrosis and bile duct proliferation. S100B was mainly present in bile duct epithelial cells, and its expression was upregulated in proportion to the ductular reaction during fibrogenesis by BDL. RAGE expression was also increased, and interestingly, triple immunofluorescence staining and transmission electron microscopy showed that both S100B and RAGE were expressed in proliferating bile duct epithelial cells and activated hepatic stellate cells (HSCs) of the BDL livers. In addition, in rat HSCs (HSC-T6), treatment with recombinant S100B protein significantly increased fibrotic markers in a dose-dependent manner, and RAGE small interfering RNA (siRNA) suppressed S100B-stimulated upregulation of fibrotic markers compared with cells treated with scramble siRNA and S100B. CONCLUSION: These findings suggest that the increased expression of S100B and RAGE and the interaction between S100B and RAGE may play an important role in ductular reaction and liver fibrosis induced by BDL. The Korean Academy of Medical Sciences 2021-03-19 /pmc/articles/PMC8042478/ /pubmed/33847081 http://dx.doi.org/10.3346/jkms.2021.36.e90 Text en © 2021 The Korean Academy of Medical Sciences. https://creativecommons.org/licenses/by-nc/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (https://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Article
Park, Ji-Won
Kim, Mo-Jong
Kim, Sung-Eun
Kim, Hee-Jun
Jeon, Yong-Chul
Shin, Hae-Young
Park, Se Jin
Jang, Myoung-Kuk
Kim, Dong-Joon
Park, Choong-Kee
Choi, Eun-Kyoung
Increased Expression of S100B and RAGE in a Mouse Model of Bile Duct Ligation-induced Liver Fibrosis
title Increased Expression of S100B and RAGE in a Mouse Model of Bile Duct Ligation-induced Liver Fibrosis
title_full Increased Expression of S100B and RAGE in a Mouse Model of Bile Duct Ligation-induced Liver Fibrosis
title_fullStr Increased Expression of S100B and RAGE in a Mouse Model of Bile Duct Ligation-induced Liver Fibrosis
title_full_unstemmed Increased Expression of S100B and RAGE in a Mouse Model of Bile Duct Ligation-induced Liver Fibrosis
title_short Increased Expression of S100B and RAGE in a Mouse Model of Bile Duct Ligation-induced Liver Fibrosis
title_sort increased expression of s100b and rage in a mouse model of bile duct ligation-induced liver fibrosis
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8042478/
https://www.ncbi.nlm.nih.gov/pubmed/33847081
http://dx.doi.org/10.3346/jkms.2021.36.e90
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