کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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3314456 | 1211200 | 2007 | 10 صفحه PDF | دانلود رایگان |
Background/AimsEpimorphin, expressed by hepatic stellate cells in the liver, directs normal morphogenesis in various organs. The aim of this study was to clarify the mechanism by which epimorphin functions as a morphogen in vitro.MethodsMale Balb/c mice and Sprague–Dawley rats were used. First, we explored the relationship between epimorphin expression and distribution of protease-positive cells in carbon tetrachloride-induced acute liver injury. We then examined protease levels in cultured hepatocytes and signal transduction of epimorphin. Finally, we determined the requirement for proteases and NF-κB in spheroid formation induced by epimorphin.ResultsEpimorphin expression was enhanced in injured areas during late recovery phase, in which protease-positive hepatocytes were localized adjacent to epimorphin-expressing cells. In vitro, epimorphin induced matrix metalloproteinase (MMP) 9, MMP 3 and urokinase type plasminogen activator (uPA) in hepatocytes. NF-κB mediated these protease expressions in hepatocytes. These proteases were required for epimorphin-induced and Matrigel induced spheroid. An epimorphin-neutralizing antibody also blocked spheroid formation on Matrigel, which contained epimorphin. In addition, NF-κB activation was also required for spheroid formation.ConclusionEpimorphin elicits hepatocyte spheroids by inducing proteases in rodent hepatocytes through NF-κB.
Journal: Journal of Hepatology - Volume 47, Issue 6, December 2007, Pages 834–843