SerpinB3 Promotes Pro-fibrogenic Responses in Activated Hepatic Stellate Cells
Abstract 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...
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Nature Portfolio
2017
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oai:doaj.org-article:c74e478e1eb44cac816dd0dfb0e444b32021-12-02T15:04:51ZSerpinB3 Promotes Pro-fibrogenic Responses in Activated Hepatic Stellate Cells10.1038/s41598-017-03744-32045-2322https://doaj.org/article/c74e478e1eb44cac816dd0dfb0e444b32017-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-03744-3https://doaj.org/toc/2045-2322Abstract 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 CCl4 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.Erica NovoGianmarco VillanoCristian TuratoStefania CannitoClaudia PaternostroChiara BuslettaAlessandra BiasioloSantina QuartaElisabetta MorelloClaudia BoccaAntonella MigliettaEzio DavidSalvatore SuttiMario PlebaniEmanuele AlbanoMaurizio ParolaPatrizia PontissoNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-10 (2017) |
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Medicine R Science Q Erica Novo Gianmarco Villano Cristian Turato Stefania Cannito Claudia Paternostro Chiara Busletta Alessandra Biasiolo Santina Quarta Elisabetta Morello Claudia Bocca Antonella Miglietta Ezio David Salvatore Sutti Mario Plebani Emanuele Albano Maurizio Parola Patrizia Pontisso SerpinB3 Promotes Pro-fibrogenic Responses in Activated Hepatic Stellate Cells |
| description |
Abstract 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 CCl4 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. |
| format |
article |
| author |
Erica Novo Gianmarco Villano Cristian Turato Stefania Cannito Claudia Paternostro Chiara Busletta Alessandra Biasiolo Santina Quarta Elisabetta Morello Claudia Bocca Antonella Miglietta Ezio David Salvatore Sutti Mario Plebani Emanuele Albano Maurizio Parola Patrizia Pontisso |
| author_facet |
Erica Novo Gianmarco Villano Cristian Turato Stefania Cannito Claudia Paternostro Chiara Busletta Alessandra Biasiolo Santina Quarta Elisabetta Morello Claudia Bocca Antonella Miglietta Ezio David Salvatore Sutti Mario Plebani Emanuele Albano Maurizio Parola Patrizia Pontisso |
| author_sort |
Erica Novo |
| title |
SerpinB3 Promotes Pro-fibrogenic Responses in Activated Hepatic Stellate Cells |
| title_short |
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_sort |
serpinb3 promotes pro-fibrogenic responses in activated hepatic stellate cells |
| publisher |
Nature Portfolio |
| publishDate |
2017 |
| url |
https://doaj.org/article/c74e478e1eb44cac816dd0dfb0e444b3 |
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