RNA Interference against Discoidin Domain Receptor 2 Ameliorates Alcoholic Liver Disease in Rats

• Published in: PloS one Vol. 8; no. 2; p. e55860
• Main Authors: Luo, Zheng, Liu, Huimin, Sun, Xiaomeng, Guo, Rong, Cui, Ruibing, Ma, Xiangxing, Yan, Ming
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 07.02.2013; Public Library of Science (PLoS)
• Subjects: Acetaldehyde - pharmacology; Alcohol; Alcohols; Animals; Apoptosis; Apoptosis - genetics; Biology; Cell Line; Cell Proliferation; Collagen; Collagen Type I - genetics; Collagen Type I - metabolism; Computer memory; Diabetes; Discoidin Domain Receptors; Disease Models, Animal; Electron microscopy; Extracellular matrix; Fibrosis; Gangrene; Gastroenterology; Gene expression; Gene Expression Regulation - drug effects; Genetic vectors; Geriatrics; Growth factors; Hepatic Stellate Cells - drug effects; Hepatic Stellate Cells - metabolism; Hepatitis; Hepatocytes; Hospitals; Immunohistochemistry; Kinases; Liver; Liver - metabolism; Liver - pathology; Liver cirrhosis; Liver diseases; Liver Diseases, Alcoholic - genetics; Liver Diseases, Alcoholic - metabolism; Liver Diseases, Alcoholic - pathology; Male; Matrix metalloproteinase; Matrix Metalloproteinase 2 - metabolism; Medicine; Metalloproteinase; Microscopy; Necrosis - genetics; Pathogenesis; Polymerase chain reaction; Rats; Receptor Protein-Tyrosine Kinases - genetics; Receptor Protein-Tyrosine Kinases - metabolism; Receptors, Mitogen - genetics; Receptors, Mitogen - metabolism; Ribonucleic acid; RNA; RNA Interference; RNA, Small Interfering - genetics; RNA, Small Interfering - metabolism; RNA-mediated interference; Rodents; Signal transduction; Signal Transduction - drug effects; Signaling; Tissue inhibitor of metalloproteinase 1; Tissue Inhibitor of Metalloproteinase-1 - genetics; Tissue Inhibitor of Metalloproteinase-1 - metabolism; Transfection; Transforming growth factor; Transforming Growth Factor beta1 - metabolism; China
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0055860

Discoidin domain receptor 2 (DDR2) is involved in fibrotic disease. However, the exact pathogenic implications of the receptor in early alcoholic liver disease are still controversial. We constructed plasmid vectors encoding short-hairpin RNA against DDR2 to investigate its role in alcoholic liver disease in an immortalized rat hepatic stellate cell line, HSC-T6, and in rats by MTT, RT-PCR and western blot analyses; immunohistochemistry and electron microscopy. Alcohol-induced upregulation of DDR2 was associated with the expression of matrix metalloproteinase 2, the transforming growth factor β1 signaling pathway and tissue inhibitor of metalloproteinase 1; collagen deposition; and extracellular matrix remodeling. Inhibition of DDR2 decreased HSC-T6 cell proliferation and liver injury in rats with 10-week-induced alcoholic liver disease. DDR2 may have an important role in the pathogenesis of early-stage alcoholic liver disease. Silencing DDR2 may be effective in preventing early-stage alcoholic liver disease.