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Extracellular matrix regulation of hepatic transcription factors is dependent on cell structure
Author(s) -
Schuetz Erin G.
Publication year - 1992
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1002/hep.1840150638
Subject(s) - extracellular matrix , enhancer , transcription factor , microbiology and biotechnology , hepatocyte nuclear factor 4 , biology , cell culture , cellular differentiation , regulation of gene expression , transcriptional regulation , cell , gene expression , transfection , hepatic stellate cell , liver cell , chemistry , gene , biochemistry , genetics , medicine , endocrinology , nuclear receptor
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, HNF3α 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 HNF3α 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.