RNA Interference against Discoidin Domain Receptor 2 Ameliorates Alcoholic Liver Disease in Rats
نویسندگان
چکیده
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.
منابع مشابه
RNA interference for discoidin domain receptor 2 attenuates neointimal formation in balloon injured rat carotid artery.
OBJECTIVE Discoidin domain receptor 2 (DDR2) plays potential roles in the regulation of collagen turnover mediated by smooth muscle cells (SMCs) in atherosclerosis. Little is known about the function of DDR2 in vascular system. We investigated whether inhibition of DDR2 by small interfering RNA (siRNA) can reduce neointimal formation after arterial injury. METHODS AND RESULTS SMCs from thorac...
متن کاملLetter of retraction: Suppression of discoidin domain receptor 1 by RNA interference attenuates lung inflammation.
Discoidin domain receptor 1 (DDR1) is a receptor tyrosine kinase whose ligand is collagen. Recently, we have reported the association of DDR1 in the cytokine production of human leukocytes in in vitro and in vivo expression in idiopathic pulmonary fibrosis. However, its role in in vivo inflammation has not been fully elucidated. Small interference RNA (siRNA) can induce specific suppression of ...
متن کاملEpigallocatechin-3-Gallate Ameliorates Alcohol-Induced Liver Injury in Rats
Endotoxemia is a common event in alcoholic liver disease. Elevated intestinal permeability is the major factor involved in the mechanism of alcoholic endotoxemia and the pathogenesis of alcoholic liver disease. This study examined the effect of epigallocatechin-3-gallate (EGCG) on alcohol-induced gut leakiness, and explored the related mechanisms involved in its protection against alcohol-induc...
متن کاملSuppression of Discoidin Domain Receptor 1 by RNA Interference Attenuates Lung Inflammation
متن کامل
Discoidin domain receptor 1 contributes to eosinophil survival in an NF- B–dependent manner in Churg-Strauss syndrome
Churg-Strauss syndrome (CSS) is a systemic disease that shows marked eosinophilia along with eosinophil infiltration in the tissue. Prolonged eosinophil survival plays an important role in the pathogenesis of CSS; however, its detailed molecular mechanism remains unclear. Discoidin domain receptor 1 (DDR1) is a receptor tyrosine kinase, and its ligand is collagen. DDR1 was expressed in human le...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
عنوان ژورنال:
دوره 8 شماره
صفحات -
تاریخ انتشار 2013