RNA interference against discoidin domain receptor 2 ameliorates alcoholic liver disease in rats.

Abstract

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.

• Authors: Zheng Luo, Huimin Liu, Xiaomeng Sun, Rong Guo, Ruibing Cui, Xiangxing Ma, Ming Yan
• Journal: PloS one (PLoS One) Vol. 8 Issue 2 Pg. e55860 ( 2013) ISSN: 1932-6203 [Electronic] United States
• PMID: 23409069 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Collagen Type I
• RNA, Small Interfering
• Receptors, Mitogen
• Tissue Inhibitor of Metalloproteinase-1
• Transforming Growth Factor beta1
• Discoidin Domain Receptors
• Receptor Protein-Tyrosine Kinases
• Matrix Metalloproteinase 2
• Acetaldehyde

Topics

• Acetaldehyde (pharmacology)
• Animals
• Apoptosis (genetics)
• Cell Line
• Cell Proliferation
• Collagen Type I (genetics, metabolism)
• Discoidin Domain Receptors
• Disease Models, Animal
• Gene Expression Regulation (drug effects)
• Hepatic Stellate Cells (drug effects, metabolism)
• Liver (metabolism, pathology)
• Liver Diseases, Alcoholic (genetics, metabolism, pathology)
• Male
• Matrix Metalloproteinase 2 (metabolism)
• Necrosis (genetics)
• RNA Interference
• RNA, Small Interfering (genetics, metabolism)
• Rats
• Receptor Protein-Tyrosine Kinases (genetics, metabolism)
• Receptors, Mitogen (genetics, metabolism)
• Signal Transduction (drug effects)
• Tissue Inhibitor of Metalloproteinase-1 (genetics, metabolism)
• Transfection
• Transforming Growth Factor beta1 (metabolism)