Prolonged silencing of diacylglycerol acyltransferase-1 induces a dedifferentiated phenotype in human liver cells.
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 β1 in patients who have nodular cirrhosis without fatty degeneration.
Department of Bio and Brain Engineering, KAIST, Daejeon, Korea.
Soyoung
S
Chang
Laboratory of Immunology and Infectious Diseases, Graduate School of Medical Science and Engineering, KAIST, Daejeon, Korea.
Pil Soo
PS
Sung
Department of Bio and Brain Engineering, KAIST, Daejeon, Korea.
Jungsul
J
Lee
Department of Bio and Brain Engineering, KAIST, Daejeon, Korea.
Junseong
J
Park
Laboratory of Immunology and Infectious Diseases, Graduate School of Medical Science and Engineering, KAIST, Daejeon, Korea.
Eui-Cheol
EC
Shin
Department of Bio and Brain Engineering, KAIST, Daejeon, Korea.|KAIST Institute for the BioCentury, KAIST, Daejeon, Korea.
Chulhee
http://orcid.org/0000-0001-5542-9136
C
Choi
D015815:Cell Adhesion Molecules / Q000378:metabolism; D054337:Cell Dedifferentiation; D051048:Diacylglycerol O-Acyltransferase / Q000235:genetics* / Q000378:metabolism; D015536:Down-Regulation; D004794:Enzyme Repression; D015870:Gene Expression; D055785:Gene Knockdown Techniques; D056945:Hep G2 Cells; D022781:Hepatocytes / Q000201:enzymology; D006801:Humans; D008099:Liver / Q000201:enzymology* / Q000473:pathology; D008103:Liver Cirrhosis / Q000201:enzymology; D010641:Phenotype; D034741:RNA, Small Interfering / Q000235:genetics; D013234:Stem Cells / Q000201:enzymology
D015815:Cell Adhesion Molecules; D034741:RNA, Small Interfering; C494881:DGAT1 protein, human; D051048:Diacylglycerol O-Acyltransferase
cirrhosis; diacylglycerol acyltransferase-1; gene silencing; stem cell-like phenotype