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SerpinB3 Promotes Pro-fibrogenic Responses in Activated Hepatic Stellate Cells

SerpinB3 is a hypoxia- and hypoxia-inducible factor-2α-dependent cystein protease inhibitor that is up-regulated in hepatocellular carcinoma and in parenchymal cells during chronic liver diseases (CLD). SerpinB3 up-regulation in CLD patients has been reported to correlate with the extent of liver fi...

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Autores principales: Novo, Erica, Villano, Gianmarco, Turato, Cristian, Cannito, Stefania, Paternostro, Claudia, Busletta, Chiara, Biasiolo, Alessandra, Quarta, Santina, Morello, Elisabetta, Bocca, Claudia, Miglietta, Antonella, David, Ezio, Sutti, Salvatore, Plebani, Mario, Albano, Emanuele, Parola, Maurizio, Pontisso, Patrizia
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5469760/
https://www.ncbi.nlm.nih.gov/pubmed/28611447
http://dx.doi.org/10.1038/s41598-017-03744-3
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author Novo, Erica
Villano, Gianmarco
Turato, Cristian
Cannito, Stefania
Paternostro, Claudia
Busletta, Chiara
Biasiolo, Alessandra
Quarta, Santina
Morello, Elisabetta
Bocca, Claudia
Miglietta, Antonella
David, Ezio
Sutti, Salvatore
Plebani, Mario
Albano, Emanuele
Parola, Maurizio
Pontisso, Patrizia
author_facet Novo, Erica
Villano, Gianmarco
Turato, Cristian
Cannito, Stefania
Paternostro, Claudia
Busletta, Chiara
Biasiolo, Alessandra
Quarta, Santina
Morello, Elisabetta
Bocca, Claudia
Miglietta, Antonella
David, Ezio
Sutti, Salvatore
Plebani, Mario
Albano, Emanuele
Parola, Maurizio
Pontisso, Patrizia
author_sort Novo, Erica
collection PubMed
description SerpinB3 is a hypoxia- and hypoxia-inducible factor-2α-dependent cystein protease inhibitor that is up-regulated in hepatocellular carcinoma and in parenchymal cells during chronic liver diseases (CLD). SerpinB3 up-regulation in CLD patients has been reported to correlate with the extent of liver fibrosis and the production of transforming growth factor-β1, but the actual role of SerpinB3 in hepatic fibrogenesis is still poorly characterized. In the present study we analyzed the pro-fibrogenic action of SerpinB3 in cell cultures and in two different murine models of liver fibrosis. “In vitro” experiments revealed that SerpinB3 addition to either primary cultures of human activated myofibroblast-like hepatic stellate cells (HSC/MFs) or human stellate cell line (LX2 cells) strongly up-regulated the expression of genes involved in fibrogenesis and promoted oriented migration, but not cell proliferation. Chronic liver injury by CCl(4) administration or by feeding a methionine/choline deficient diet to transgenic mice over-expressing human SerpinB3 in hepatocytes confirmed that SerpinB3 over-expression significantly increased the mRNA levels of pro-fibrogenic genes, collagen deposition and αSMA-positive HSC/MFs as compared to wild-type mice, without affecting parenchymal damage. The present study provides for the first time evidence that hepatocyte release of SerpinB3 during CLD can contribute to liver fibrogenesis by acting on HSC/MFs.
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spelling pubmed-54697602017-06-19 SerpinB3 Promotes Pro-fibrogenic Responses in Activated Hepatic Stellate Cells Novo, Erica Villano, Gianmarco Turato, Cristian Cannito, Stefania Paternostro, Claudia Busletta, Chiara Biasiolo, Alessandra Quarta, Santina Morello, Elisabetta Bocca, Claudia Miglietta, Antonella David, Ezio Sutti, Salvatore Plebani, Mario Albano, Emanuele Parola, Maurizio Pontisso, Patrizia Sci Rep Article SerpinB3 is a hypoxia- and hypoxia-inducible factor-2α-dependent cystein protease inhibitor that is up-regulated in hepatocellular carcinoma and in parenchymal cells during chronic liver diseases (CLD). SerpinB3 up-regulation in CLD patients has been reported to correlate with the extent of liver fibrosis and the production of transforming growth factor-β1, but the actual role of SerpinB3 in hepatic fibrogenesis is still poorly characterized. In the present study we analyzed the pro-fibrogenic action of SerpinB3 in cell cultures and in two different murine models of liver fibrosis. “In vitro” experiments revealed that SerpinB3 addition to either primary cultures of human activated myofibroblast-like hepatic stellate cells (HSC/MFs) or human stellate cell line (LX2 cells) strongly up-regulated the expression of genes involved in fibrogenesis and promoted oriented migration, but not cell proliferation. Chronic liver injury by CCl(4) administration or by feeding a methionine/choline deficient diet to transgenic mice over-expressing human SerpinB3 in hepatocytes confirmed that SerpinB3 over-expression significantly increased the mRNA levels of pro-fibrogenic genes, collagen deposition and αSMA-positive HSC/MFs as compared to wild-type mice, without affecting parenchymal damage. The present study provides for the first time evidence that hepatocyte release of SerpinB3 during CLD can contribute to liver fibrogenesis by acting on HSC/MFs. Nature Publishing Group UK 2017-06-13 /pmc/articles/PMC5469760/ /pubmed/28611447 http://dx.doi.org/10.1038/s41598-017-03744-3 Text en © The Author(s) 2017 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
Novo, Erica
Villano, Gianmarco
Turato, Cristian
Cannito, Stefania
Paternostro, Claudia
Busletta, Chiara
Biasiolo, Alessandra
Quarta, Santina
Morello, Elisabetta
Bocca, Claudia
Miglietta, Antonella
David, Ezio
Sutti, Salvatore
Plebani, Mario
Albano, Emanuele
Parola, Maurizio
Pontisso, Patrizia
SerpinB3 Promotes Pro-fibrogenic Responses in Activated Hepatic Stellate Cells
title SerpinB3 Promotes Pro-fibrogenic Responses in Activated Hepatic Stellate Cells
title_full SerpinB3 Promotes Pro-fibrogenic Responses in Activated Hepatic Stellate Cells
title_fullStr SerpinB3 Promotes Pro-fibrogenic Responses in Activated Hepatic Stellate Cells
title_full_unstemmed SerpinB3 Promotes Pro-fibrogenic Responses in Activated Hepatic Stellate Cells
title_short SerpinB3 Promotes Pro-fibrogenic Responses in Activated Hepatic Stellate Cells
title_sort serpinb3 promotes pro-fibrogenic responses in activated hepatic stellate cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5469760/
https://www.ncbi.nlm.nih.gov/pubmed/28611447
http://dx.doi.org/10.1038/s41598-017-03744-3
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