Antifibrotic Effect of Smad Decoy Oligodeoxynucleotide in a CCl₄-Induced Hepatic Fibrosis Animal Model

• Published in: Molecules (Basel, Switzerland) Vol. 23; no. 8; p. 1991
• Main Authors: Gwon, Mi-Gyeong, Kim, Jung-Yeon, An, Hyun-Jin, Kim, Woon-Hae, Gu, Hyemin, Kim, Min-Kyung, Park, Sok Cheon, Park, Kwan-Kyu
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 10.08.2018; MDPI
• Subjects: Animals; Base Sequence; Carbon tetrachloride; Carbon Tetrachloride - adverse effects; CCl4; decoy; Demolition; Deoxyribonucleic acid; Disease Models, Animal; DNA; Epithelial-Mesenchymal Transition - drug effects; Epithelial-Mesenchymal Transition - genetics; Epithelium; Extracellular Matrix - metabolism; Fibrosis; Hepatocellular carcinoma; Liver - drug effects; Liver - metabolism; Liver - pathology; Liver Cirrhosis - chemically induced; Liver Cirrhosis - drug therapy; Liver Cirrhosis - metabolism; Liver Cirrhosis - pathology; Liver diseases; liver fibrosis; Male; Mesenchyme; Mice; Nucleotide sequence; oligodeoxynucleotide; Oligodeoxyribonucleotides - chemical synthesis; Oligodeoxyribonucleotides - chemistry; Oligodeoxyribonucleotides - pharmacology; Phenotypes; Proteins; Rodents; Signal Transduction - drug effects; Smad; Smad protein; Smad Proteins - chemistry; Smad Proteins - genetics; Smad Proteins - metabolism; Transfection; Wound healing; liver fibrosis; Smad; decoy; oligodeoxynucleotide; CCl4
• ISSN: 1420-3049; 1420-3049
• DOI: 10.3390/molecules23081991

Hepatic fibrosis is the wound-healing process of chronic hepatic disease that leads to the end-stage of hepatocellular carcinoma and demolition of hepatic structures. Epithelial⁻mesenchymal transition (EMT) has been identified to phenotypic conversion of the epithelium to mesenchymal phenotype that occurred during fibrosis. Smad decoy oligodeoxynucleotide (ODN) is a synthetic DNA fragment containing a complementary sequence of Smad transcription factor. Thus, this study evaluated the antifibrotic effects of Smad decoy ODN on carbon tetrachloride (CCl₄)-induced hepatic fibrosis in mice. As shown in histological results, CCl₄ treatment triggered hepatic fibrosis and increased Smad expression. On the contrary, Smad decoy ODN administration suppressed fibrogenesis and EMT process. The expression of Smad signaling and EMT-associated protein was markedly decreased in Smad decoy ODN-treated mice compared with CCl₄-injured mice. In conclusion, these data indicate the practicability of Smad decoy ODN administration for preventing hepatic fibrosis and EMT processes.