scholarly journals The extracellular matrix coordinately modulates liver transcription factors and hepatocyte morphology.

1991 ◽  
Vol 11 (9) ◽  
pp. 4405-4414 ◽  
Author(s):  
C M DiPersio ◽  
D A Jackson ◽  
K S Zaret
Keyword(s):  
Extracellular Matrix ◽  
Transcription Factors ◽  
Cell Line ◽  
Cell Morphology ◽  
Transcriptional Activation ◽  
Hepatoma Cell ◽  
Collagen Gel ◽  
Hepatoma Cell Line ◽  
Transcriptional Enhancer ◽  
Mrna Accumulation

The extracellular matrix (ECM) promotes tissue morphogenesis, cell migration, and the differentiation of a variety of cell types. However, the mechanisms by which ECM causes differentiated gene expression have been unknown. In this report, we show that culturing the hepatocyte-derived cell line H2.35 on an ECM gel changes cell morphology and selectively stimulates the transcription of a subset of liver-specific genes, including serum albumin. Transcriptional activation by ECM also occurs with transfected plasmids bearing the transcriptional enhancer of the albumin gene. ECM substrates of different composition activated the albumin enhancer only when the ECM promoted a cuboidal, differentiated cell morphology. Enhancer activation by the ECM was mediated by two liver transcription factors, HNF3 alpha and eH-TF, which appear to be regulated differently by matrix. Specifically, we found that a collagen gel substratum caused a selective increase in the factor HNF3 alpha at the levels of mRNA accumulation and DNA-binding activity in nuclear extracts, both in H2.35 cells and in the hepatoma cell line HepG2. We conclude that the ECM can stimulate cell differentiation by selectively activating transcriptional regulatory factors and that such regulation occurs coordinately with ECM-promoted changes in cell shape.

The extracellular matrix coordinately modulates liver transcription factors and hepatocyte morphology

1991 ◽  
Vol 11 (9) ◽  
pp. 4405-4414
Author(s):  
C M DiPersio ◽  
D A Jackson ◽  
K S Zaret
Keyword(s):  
Extracellular Matrix ◽  
Transcription Factors ◽  
Cell Line ◽  
Cell Morphology ◽  
Transcriptional Activation ◽  
Hepatoma Cell ◽  
Collagen Gel ◽  
Hepatoma Cell Line ◽  
Transcriptional Enhancer ◽  
Mrna Accumulation

The extracellular matrix (ECM) promotes tissue morphogenesis, cell migration, and the differentiation of a variety of cell types. However, the mechanisms by which ECM causes differentiated gene expression have been unknown. In this report, we show that culturing the hepatocyte-derived cell line H2.35 on an ECM gel changes cell morphology and selectively stimulates the transcription of a subset of liver-specific genes, including serum albumin. Transcriptional activation by ECM also occurs with transfected plasmids bearing the transcriptional enhancer of the albumin gene. ECM substrates of different composition activated the albumin enhancer only when the ECM promoted a cuboidal, differentiated cell morphology. Enhancer activation by the ECM was mediated by two liver transcription factors, HNF3 alpha and eH-TF, which appear to be regulated differently by matrix. Specifically, we found that a collagen gel substratum caused a selective increase in the factor HNF3 alpha at the levels of mRNA accumulation and DNA-binding activity in nuclear extracts, both in H2.35 cells and in the hepatoma cell line HepG2. We conclude that the ECM can stimulate cell differentiation by selectively activating transcriptional regulatory factors and that such regulation occurs coordinately with ECM-promoted changes in cell shape.

Transcriptional regulation of the phosphoenolpyruvate carboxykinase gene by cooperation between hepatic nuclear factors

1994 ◽  
Vol 14 (11) ◽  
pp. 7124-7133
Author(s):  
O Yanuka-Kashles ◽  
H Cohen ◽  
M Trus ◽  
A Aran ◽  
N Benvenisty ◽  
...  
Keyword(s):  
Transcriptional Regulation ◽  
Transcription Factors ◽  
Cell Line ◽  
Promoter Activity ◽  
Phosphoenolpyruvate Carboxykinase ◽  
Fetal Liver ◽  
Hepatoma Cell ◽  
Hepatoma Cell Line ◽  
Recognition Sequence ◽  
Factor C

To study the transcriptional regulation of the liver gluconeogenic phenotype, the underdifferentiated mouse Hepa-1c1c7 (Hepa) hepatoma cell line was used. These cells mimicked the fetal liver by appreciably expressing the alpha-fetoprotein and albumin genes but not the phosphoenolpyruvate carboxykinase (PEPCK) gene. Unlike the fetal liver, however, Hepa cells failed to express the early-expressed factors hepatocyte nuclear factor 1 alpha (HNF-1 alpha) and HNF-4 and the late-expressed factor C/EBP alpha, thereby providing a suitable system for examining possible cooperation between these factors in the transcriptional regulation of the PEPCK gene. Transient transfection assays of a chimeric PEPCK-chloramphenicol acetyltransferase construct showed a residual PEPCK promoter activity in the Hepa cell line, which was slightly stimulated by cotransfection with a single transcription factor from either the C/EBP family or HNF-1 alpha but not at all affected by cotransfection of HNF-4. In contrast, cotransfection of the PEPCK construct with members from the C/EBP family plus HNF-1 alpha resulted in a synergistic stimulation of the PEPCK promoter activity. This synergistic effect depended on the presence in the PEPCK promoter region of the HNF-1 recognition sequence and on the presence of two C/EBP recognition sequences. The results demonstrate a requirement for coexistence and cooperation between early and late liver-enriched transcription factors in the transcriptional regulation of the PEPCK gene. In addition, the results suggest redundancy between members of the C/EBP family of transcription factors in the regulation of PEPCK gene expression.

Insulin-Mediated Downregulation of Apolipoprotein A-I Gene in Human Hepatoma Cell Line HepG2: The Role of Interaction Between FOXO1 and LXRβ Transcription Factors

2016 ◽  
Vol 118 (2) ◽  
pp. 382-396 ◽  
Author(s):  
Vladimir S. Shavva ◽  
Alexandra M. Bogomolova ◽  
Artemy A. Nikitin ◽  
Ella B. Dizhe ◽  
Dmitry A. Tanyanskiy ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Cell Line ◽  
Hepatoma Cell ◽  
Hepatoma Cell Line ◽  
Human Hepatoma ◽  
Human Hepatoma Cell ◽  
Apolipoprotein A ◽  
Hepatoma Cell Line Hepg2 ◽  
I Gene

scholarly journals Transcriptional regulation of the phosphoenolpyruvate carboxykinase gene by cooperation between hepatic nuclear factors.

1994 ◽  
Vol 14 (11) ◽  
pp. 7124-7133 ◽  
Author(s):  
O Yanuka-Kashles ◽  
H Cohen ◽  
M Trus ◽  
A Aran ◽  
N Benvenisty ◽  
...  
Keyword(s):  
Transcriptional Regulation ◽  
Transcription Factors ◽  
Cell Line ◽  
Promoter Activity ◽  
Phosphoenolpyruvate Carboxykinase ◽  
Fetal Liver ◽  
Hepatoma Cell ◽  
Hepatoma Cell Line ◽  
Recognition Sequence ◽  
Factor C

To study the transcriptional regulation of the liver gluconeogenic phenotype, the underdifferentiated mouse Hepa-1c1c7 (Hepa) hepatoma cell line was used. These cells mimicked the fetal liver by appreciably expressing the alpha-fetoprotein and albumin genes but not the phosphoenolpyruvate carboxykinase (PEPCK) gene. Unlike the fetal liver, however, Hepa cells failed to express the early-expressed factors hepatocyte nuclear factor 1 alpha (HNF-1 alpha) and HNF-4 and the late-expressed factor C/EBP alpha, thereby providing a suitable system for examining possible cooperation between these factors in the transcriptional regulation of the PEPCK gene. Transient transfection assays of a chimeric PEPCK-chloramphenicol acetyltransferase construct showed a residual PEPCK promoter activity in the Hepa cell line, which was slightly stimulated by cotransfection with a single transcription factor from either the C/EBP family or HNF-1 alpha but not at all affected by cotransfection of HNF-4. In contrast, cotransfection of the PEPCK construct with members from the C/EBP family plus HNF-1 alpha resulted in a synergistic stimulation of the PEPCK promoter activity. This synergistic effect depended on the presence in the PEPCK promoter region of the HNF-1 recognition sequence and on the presence of two C/EBP recognition sequences. The results demonstrate a requirement for coexistence and cooperation between early and late liver-enriched transcription factors in the transcriptional regulation of the PEPCK gene. In addition, the results suggest redundancy between members of the C/EBP family of transcription factors in the regulation of PEPCK gene expression.

Endothelial Cell Protein S Synthesis Is Upregulated by the Complex of IL-6 and Soluble IL-6 Receptor

1997 ◽  
Vol 77 (05) ◽  
pp. 1014-1019 ◽  
Author(s):  
W Craig Hooper ◽  
Donald J Phillips ◽  
Bruce L Evatt
Keyword(s):  
Endothelial Cells ◽  
Endothelial Cell ◽  
Cell Line ◽  
Neutralizing Antibodies ◽  
Hepatoma Cell ◽  
Protein S ◽  
Oncostatin M ◽  
Cell Protein ◽  
Microvascular Endothelial Cell ◽  
Hepatoma Cell Line

SummaryWe have recently demonstrated that the proinflammatory cytokine, interleukin-6 (IL-6), could upregulate the production of protein S in the human hepatoma cell line, HepG-2, but not in endothelial cells. In this study, we have demonstrated that the combination of exogenous IL-6 and soluble IL-6 receptor (sIL-6R) could significantly upregulate protein S production in both primary human umbilical vein endothelial cells (HUVEC) and in the immortalized human microvascular endothelial cell line, HMEC-1. The IL-6/sIL-6R complex was also able to rapidly induce tyrosine phosphorylation of the IL-6 transducer, gpl30. Neutralizing antibodies directed against either IL-6 or gpl30 blocked protein S upregulation by the IL-6/sIL-6R complex. It was also observed that exogenous sIL-6R could also upregulate protein S by forming a complex with IL-6 constitutively produced by the endothelial cell. Two other cytokines which also utilize the gpl30 receptor, oncostatin M (OSM) and leukemia inhibitory factor (LIF), were also able to upregulate endothelial cell protein S. This study demonstrates a mechanism that allows endothelial cells to respond to IL-6 and also illustrates the potential importance of circulating soluble receptors in the regulation of the anticoagulation pathway.

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