4.5 Article

Prolonged silencing of diacylglycerol acyltransferase-1 induces a dedifferentiated phenotype in human liver cells

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出版社

WILEY
DOI: 10.1111/jcmm.12685

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diacylglycerol acyltransferase-1; gene silencing; stem cell-like phenotype; cirrhosis

资金

  1. Global Frontier Program through the National Research Foundation of Korea (NRF) - Ministry of Science, ICT Future Plannig [2014M3A6A8063924]

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Diacylglycerol acyltransferase-1 (DGAT1), a key enzyme in triglyceride (TG) biogenesis, is highly associated with metabolic abnormalities, such as obesity and type 2 diabetes. However, the effects of DGAT1 silencing in the human liver have not been elucidated. To investigate the effects of DGAT1 silencing in human liver cells, we compared the cellular behaviours of DGAT1-deficient Huh-7.5 cell lines with those of control Huh-7.5 cells. DGAT1-deficient cells acquired dedifferentiated and stem cell-like characteristics, such as formation of aggregates in the presence of high levels of growth factors, high proliferation rates and loss of albumin secretion. In relation to aggregate formation, the expression level of various adhesion molecules was significantly altered in DGAT1-deficient cells. Microarray data analysis and immunostaining of patient tissue samples clearly showed decreased expression levels of DGAT1 and integrin beta 1 in patients who have nodular cirrhosis without fatty degeneration.

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