Anti-fibrotic Effects of Synthetic Oligodeoxynucleotide for TGF-β1 and Smad in an Animal Model of Liver Cirrhosis
Liver fibrosis is characterized by changes in tissue architecture and extracellular matrix composition. Liver fibrosis affects not only hepatocytes but also the non-parenchymal cells such as hepatic stellate cells (HSCs), which are essential for maintaining an intact liver structure and function. Tr...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2017-09-01
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| Series: | Molecular Therapy: Nucleic Acids |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2162253117302093 |
| _version_ | 1819084059665498112 |
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| author | Jung-Yeon Kim Hyun-Jin An Woon-Hae Kim Mi-Gyeong Gwon Hyemin Gu Yoon-Yub Park Kwan-Kyu Park |
| author_facet | Jung-Yeon Kim Hyun-Jin An Woon-Hae Kim Mi-Gyeong Gwon Hyemin Gu Yoon-Yub Park Kwan-Kyu Park |
| author_sort | Jung-Yeon Kim |
| collection | DOAJ |
| description | Liver fibrosis is characterized by changes in tissue architecture and extracellular matrix composition. Liver fibrosis affects not only hepatocytes but also the non-parenchymal cells such as hepatic stellate cells (HSCs), which are essential for maintaining an intact liver structure and function. Transforming growth factor β1 (TGF-β1) is a multifunctional cytokine that induces liver fibrosis through activation of Smad signaling pathways. To improve a new therapeutic approach, synthetic TGF-β1/Smad oligodeoxynucleotide (ODN) was used to suppress both TGF-β1 expression and Smad transcription factor using a combination of antisense ODN and decoy ODN. The aims of this study are to investigate the anti-fibrotic effects of TGF-β1/Smad ODN on simultaneous suppressions of both Smad transcription factor and TGF-β1 mRNA expression in the hepatic fibrosis model in vitro and in vivo. Synthetic TGF-β1/Smad ODN effectively inhibits Smad binding activity and TGF-β1 expression. TGF-β1/Smad ODN attenuated the epithelial mesenchymal transition (EMT) and activation of HSCs in TGF-β1-induced AML12 and HSC-T6 cells. TGF-β1/Smad ODN prevented the fibrogenesis and deposition of collagen in CCl4-treated mouse model. Synthetic TGF-β1/Smad ODN demonstrates anti-fibrotic effects that are mediated by the suppression of fibrogenic protein and inflammatory cytokines. Therefore, synthetic TGF-β1/Smad ODN has substantial therapeutic feasibility for the treatment of liver fibrotic diseases. Keywords: oligodeoxynucleotide, decoy, antisense, liver fibrosis, TGF-β1, Smad |
| first_indexed | 2024-12-21T20:42:27Z |
| format | Article |
| id | doaj.art-7a71440ad1334e8c974c229e8bec65f4 |
| institution | Directory Open Access Journal |
| issn | 2162-2531 |
| language | English |
| last_indexed | 2024-12-21T20:42:27Z |
| publishDate | 2017-09-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Molecular Therapy: Nucleic Acids |
| spelling | doaj.art-7a71440ad1334e8c974c229e8bec65f42022-12-21T18:50:55ZengElsevierMolecular Therapy: Nucleic Acids2162-25312017-09-018250263Anti-fibrotic Effects of Synthetic Oligodeoxynucleotide for TGF-β1 and Smad in an Animal Model of Liver CirrhosisJung-Yeon Kim0Hyun-Jin An1Woon-Hae Kim2Mi-Gyeong Gwon3Hyemin Gu4Yoon-Yub Park5Kwan-Kyu Park6Department of Pathology, College of Medicine, Catholic University of Daegu, Daegu 42472, Republic of KoreaDepartment of Pathology, College of Medicine, Catholic University of Daegu, Daegu 42472, Republic of KoreaDepartment of Pathology, College of Medicine, Catholic University of Daegu, Daegu 42472, Republic of KoreaDepartment of Pathology, College of Medicine, Catholic University of Daegu, Daegu 42472, Republic of KoreaDepartment of Pathology, College of Medicine, Catholic University of Daegu, Daegu 42472, Republic of KoreaDepartment of Physiology, College of Medicine, Catholic University of Daegu, Daegu 42472, Republic of KoreaDepartment of Pathology, College of Medicine, Catholic University of Daegu, Daegu 42472, Republic of Korea; Corresponding author: Kwan-Kyu Park, MD, PhD, Department of Pathology, School of Medicine, Catholic University of Daegu, Daegu 42472, Republic of Korea.Liver fibrosis is characterized by changes in tissue architecture and extracellular matrix composition. Liver fibrosis affects not only hepatocytes but also the non-parenchymal cells such as hepatic stellate cells (HSCs), which are essential for maintaining an intact liver structure and function. Transforming growth factor β1 (TGF-β1) is a multifunctional cytokine that induces liver fibrosis through activation of Smad signaling pathways. To improve a new therapeutic approach, synthetic TGF-β1/Smad oligodeoxynucleotide (ODN) was used to suppress both TGF-β1 expression and Smad transcription factor using a combination of antisense ODN and decoy ODN. The aims of this study are to investigate the anti-fibrotic effects of TGF-β1/Smad ODN on simultaneous suppressions of both Smad transcription factor and TGF-β1 mRNA expression in the hepatic fibrosis model in vitro and in vivo. Synthetic TGF-β1/Smad ODN effectively inhibits Smad binding activity and TGF-β1 expression. TGF-β1/Smad ODN attenuated the epithelial mesenchymal transition (EMT) and activation of HSCs in TGF-β1-induced AML12 and HSC-T6 cells. TGF-β1/Smad ODN prevented the fibrogenesis and deposition of collagen in CCl4-treated mouse model. Synthetic TGF-β1/Smad ODN demonstrates anti-fibrotic effects that are mediated by the suppression of fibrogenic protein and inflammatory cytokines. Therefore, synthetic TGF-β1/Smad ODN has substantial therapeutic feasibility for the treatment of liver fibrotic diseases. Keywords: oligodeoxynucleotide, decoy, antisense, liver fibrosis, TGF-β1, Smadhttp://www.sciencedirect.com/science/article/pii/S2162253117302093 |
| spellingShingle | Jung-Yeon Kim Hyun-Jin An Woon-Hae Kim Mi-Gyeong Gwon Hyemin Gu Yoon-Yub Park Kwan-Kyu Park Anti-fibrotic Effects of Synthetic Oligodeoxynucleotide for TGF-β1 and Smad in an Animal Model of Liver Cirrhosis Molecular Therapy: Nucleic Acids |
| title | Anti-fibrotic Effects of Synthetic Oligodeoxynucleotide for TGF-β1 and Smad in an Animal Model of Liver Cirrhosis |
| title_full | Anti-fibrotic Effects of Synthetic Oligodeoxynucleotide for TGF-β1 and Smad in an Animal Model of Liver Cirrhosis |
| title_fullStr | Anti-fibrotic Effects of Synthetic Oligodeoxynucleotide for TGF-β1 and Smad in an Animal Model of Liver Cirrhosis |
| title_full_unstemmed | Anti-fibrotic Effects of Synthetic Oligodeoxynucleotide for TGF-β1 and Smad in an Animal Model of Liver Cirrhosis |
| title_short | Anti-fibrotic Effects of Synthetic Oligodeoxynucleotide for TGF-β1 and Smad in an Animal Model of Liver Cirrhosis |
| title_sort | anti fibrotic effects of synthetic oligodeoxynucleotide for tgf β1 and smad in an animal model of liver cirrhosis |
| url | http://www.sciencedirect.com/science/article/pii/S2162253117302093 |
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