title: 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: Department of Geriatric Gastroenterology, Qilu Hospital of Shandong University, Jinan, Shandong, China.
authors: Zheng
authors: Z
authors: Luo
authors: Huimin
authors: H
authors: Liu
authors: Xiaomeng
authors: X
authors: Sun
authors: Rong
authors: R
authors: Guo
authors: Ruibing
authors: R
authors: Cui
authors: Xiangxing
authors: X
authors: Ma
authors: Ming
authors: M
authors: Yan
mesh_terms: D000079:Acetaldehyde / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis / Q000235:genetics; D002460:Cell Line; D049109:Cell Proliferation; D024042:Collagen Type I / Q000235:genetics / Q000378:metabolism; D000070818:Discoidin Domain Receptors; D004195:Disease Models, Animal; D005786:Gene Expression Regulation / Q000187:drug effects; D055166:Hepatic Stellate Cells / Q000187:drug effects / Q000378:metabolism; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008108:Liver Diseases, Alcoholic / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D009336:Necrosis / Q000235:genetics; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D051381:Rats; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics* / Q000378:metabolism; D011975:Receptors, Mitogen / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000235:genetics / Q000378:metabolism; D014162:Transfection; D053773:Transforming Growth Factor beta1 / Q000378:metabolism
chemical_list: D024042:Collagen Type I; D034741:RNA, Small Interfering; D011975:Receptors, Mitogen; D019715:Tissue Inhibitor of Metalloproteinase-1; D053773:Transforming Growth Factor beta1; D000070818:Discoidin Domain Receptors; D020794:Receptor Protein-Tyrosine Kinases; D020778:Matrix Metalloproteinase 2; D000079:Acetaldehyde