NF-kappaB activates fibronectin gene expression in rat hepatocytes

Biochem Biophys Res Commun. 2002 Oct 11;297(5):1218-24. doi: 10.1016/s0006-291x(02)02356-2.


Fibronectin (FN) plays a role in various biological processes such as fibrosis and tumor metastasis. In this study, we investigated the regulation of FN gene expression by NF-kappaB transcription factor. Transient expression of NF-kappaB p65 increased FN promoter activity in rat hepatocytes. Deletion analysis of FN promoter localized the NF-kappaB-responsive region at the position between -1214 and -1126. Mutations in a putative NF-kappaB element (5(')-GAGAATTTCC-3(')) at -1180 blocked most of the p65-induced promoter activity. Electromobility shift assays showed that the expression of p65 induced the binding of the p65/p65 homodimer to the NF-kappaB site at -1180. Stably p65-expressing cells showed increase of promoter activity, FN protein, and its mRNA levels over control cells. Furthermore, treatment of cells with interleukin-1beta, a NF-kappaB-stimulating cytokine, also increased promoter activity, FN production, and mRNA levels. These results show that NF-kappaB activates FN gene expression by binding to the responsive element at -1180 as the p65/p65 homodimer in rat hepatocytes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Binding Sites
  • Blotting, Northern
  • Blotting, Western
  • Cells, Cultured
  • Fibronectins / biosynthesis*
  • Gene Deletion
  • Gene Expression Regulation
  • Hepatocytes / metabolism*
  • Interleukin-1 / metabolism
  • Liver / metabolism
  • Luciferases / metabolism
  • Mutation
  • NF-kappa B / metabolism
  • NF-kappa B / physiology*
  • Plasmids / metabolism
  • Promoter Regions, Genetic
  • Protein Binding
  • RNA, Messenger / metabolism
  • Rats
  • Transcription Factor RelA
  • Transfection


  • Fibronectins
  • Interleukin-1
  • NF-kappa B
  • RNA, Messenger
  • Transcription Factor RelA
  • Luciferases