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Anti-fibrotic Effects of Synthetic Oligodeoxynucleotide for TGF-?1 and Smad in an Animal Model of Liver Cirrhosis.

ABSTRACT: 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 ?1 (TGF-?1) is a multifunctional cytokine that induces liver fibrosis through activation of Smad signaling pathways. To improve a new therapeutic approach, synthetic TGF-?1/Smad oligodeoxynucleotide (ODN) was used to suppress both TGF-?1 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-?1/Smad ODN on simultaneous suppressions of both Smad transcription factor and TGF-?1 mRNA expression in the hepatic fibrosis model in vitro and in vivo. Synthetic TGF-?1/Smad ODN effectively inhibits Smad binding activity and TGF-?1 expression. TGF-?1/Smad ODN attenuated the epithelial mesenchymal transition (EMT) and activation of HSCs in TGF-?1-induced AML12 and HSC-T6 cells. TGF-?1/Smad ODN prevented the fibrogenesis and deposition of collagen in CCl₄-treated mouse model. Synthetic TGF-?1/Smad ODN demonstrates anti-fibrotic effects that are mediated by the suppression of fibrogenic protein and inflammatory cytokines. Therefore, synthetic TGF-?1/Smad ODN has substantial therapeutic feasibility for the treatment of liver fibrotic diseases.

SUBMITTER: Kim JY

PROVIDER: S-EPMC5511593 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature

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Anti-fibrotic Effects of Synthetic Oligodeoxynucleotide for TGF-β1 and Smad in an Animal Model of Liver Cirrhosis.

Kim Jung-Yeon JY An Hyun-Jin HJ Kim Woon-Hae WH Gwon Mi-Gyeong MG Gu Hyemin H Park Yoon-Yub YY Park Kwan-Kyu KK

Molecular therapy. Nucleic acids 20170703

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/Sm ...[more]

PMID: 28918026

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Dataset Information

Anti-fibrotic Effects of Synthetic Oligodeoxynucleotide for TGF-?1 and Smad in an Animal Model of Liver Cirrhosis.

Publications

Anti-fibrotic Effects of Synthetic Oligodeoxynucleotide for TGF-β1 and Smad in an Animal Model of Liver Cirrhosis.

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