Class C1 decoy oligodeoxynucleotide inhibits profibrotic genes expression in rat hepatic stellate cells.

Abstract

The aim of the present study was to investigate whether class C1 decoy oligodeoxynucleotides (ODNs) can inhibit the expression of pro‑fibrotic genes associated with rat hepatic stellate cell (HSC) activation and hepatic fibrosis. Luciferase reporter assays were performed to test the promoter activities of transforming growth factor (TGF)‑β and its downstream target genes following transfection of decoy ODNs and plasmids into HSC‑T6 cells, and western blot assays were performed to measure the protein expression of those genes following decoy ODN transfection. Class C1 decoy ODNs were confirmed to inhibit the promoter activity of TGF‑β and its downstream target genes, such as type 1 collagen (COLI)α1, tissue inhibitor of metalloproteinases (TIMP)1 and α‑smooth muscle actin by Gaussia luciferase reporter assay, and to further downregulate the expression of TGF‑β, SMAD3, COLIα1 and TIMP1 by western blotting in activated HSC‑T6 cells. In conclusion, class C1 decoy ODNs inhibited pro‑fibrotic gene expression in rat HSCS by downregulating TGF‑β signaling.

• Authors: Chun Rao, Yi-Ran Ni, Yan-Min Zhao, Yan-Qiong Zhang, Rui-Ting Zhou, Chang-Bai Liu, Lin Han, Jiang-Feng Wu
• Journal: Molecular medicine reports (Mol Med Rep) Vol. 21 Issue 2 Pg. 667-674 (02 2020) ISSN: 1791-3004 [Electronic] Greece
• PMID: 31974596 (Publication Type: Journal Article)

Chemical References

• Collagen Type I
• Hes1 protein, rat
• Oligodeoxyribonucleotides
• Smad3 Protein
• Tissue Inhibitor of Metalloproteinase-1
• Transcription Factor HES-1
• Transforming Growth Factor beta

Topics

• Animals
• Cell Line
• Collagen Type I (metabolism)
• Down-Regulation (drug effects, genetics)
• Gene Expression Regulation (drug effects)
• Hepatic Stellate Cells (drug effects, metabolism, pathology)
• Liver Cirrhosis (drug therapy, genetics)
• Oligodeoxyribonucleotides (pharmacology, therapeutic use)
• Promoter Regions, Genetic (genetics)
• Rats
• Smad3 Protein (metabolism)
• Tissue Inhibitor of Metalloproteinase-1 (metabolism)
• Transcription Factor HES-1 (genetics, metabolism)
• Transforming Growth Factor beta (metabolism)