SerpinB3 Promotes Pro-fibrogenic Responses in Activated Hepatic Stellate Cells
| Autor: | Salvatore Sutti, Alessandra Biasiolo, Santina Quarta, Emanuele Albano, Claudia Bocca, Erica Novo, Maurizio Parola, Mario Plebani, Chiara Busletta, E. Morello, Cristian Turato, Antonella Miglietta, Patrizia Pontisso, Claudia Paternostro, G. Villano, Ezio David, Stefania Cannito |
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| Rok vydání: | 2017 |
| Předmět: |
Liver Cirrhosis
Genetically modified mouse medicine.medical_specialty Science CCL4 Biology Article Cell Line Mice 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Internal medicine medicine Animals Humans Choline Cells Cultured Serpins Multidisciplinary liver fibrogenesis Cell growth Hep G2 Cells Serpin B3 medicine.disease In vitro Mice Inbred C57BL medicine.anatomical_structure Endocrinology chemistry 030220 oncology & carcinogenesis Hepatocyte Hepatocellular carcinoma Cancer research Hepatic stellate cell Medicine 030211 gastroenterology & hepatology Collagen hepatic stellate cells Serpin B3 hepatic stellate cells liver fibrogenesis |
| Zdroj: | Scientific Reports Scientific Reports, Vol 7, Iss 1, Pp 1-10 (2017) |
| ISSN: | 2045-2322 |
| DOI: | 10.1038/s41598-017-03744-3 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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