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NF-kappaB activates fibronectin gene expression in rat hepatocytes
Byung-Heon Lee1, Seung-Yoon Park, Kae-Bok Kang
1Department of Biochemistry, School of Medicine, Dongguk University, 780-714, Kyungju, Republic of Korea.
Biochemical and Biophysical Research Communications
|October 10, 2002
Summary
Nuclear Factor-kappa B (NF-kappaB) activates fibronectin (FN) gene expression. This transcription factor binds to a specific DNA region, increasing FN protein and mRNA levels in rat hepatocytes.
Area of Science:
- Molecular Biology
- Cell Biology
- Biochemistry
Background:
- Fibronectin (FN) is crucial in biological processes like fibrosis and tumor metastasis.
- Understanding FN gene regulation is vital for targeting related diseases.
Purpose of the Study:
- To investigate the role of the NF-kappaB transcription factor in regulating fibronectin (FN) gene expression.
Main Methods:
- Utilized transient and stable expression systems in rat hepatocytes.
- Performed deletion analysis and site-directed mutagenesis on the FN promoter.
- Employed electromobility shift assays (EMSA) to study transcription factor binding.
Main Results:
- NF-kappaB p65 significantly increased FN promoter activity.
- Identified a key NF-kappaB-responsive element between -1214 and -1126 of the FN promoter.
- Demonstrated that p65/p65 homodimers bind to the NF-kappaB site at -1180.
- Confirmed increased FN mRNA and protein levels in p65-expressing cells and IL-1beta-treated cells.
Conclusions:
- NF-kappaB directly activates fibronectin gene expression in rat hepatocytes.
- Binding of NF-kappaB p65/p65 homodimers to the -1180 element is essential for this activation.