Affordable Access

Regulation of CFTR expression and function during differentiation of intestinal epithelial cells.

Authors
  • Sood, R
  • Bear, C
  • Auerbach, W
  • Reyes, E
  • Jensen, T
  • Kartner, N
  • Riordan, J R
  • Buchwald, M
Type
Published Article
Journal
The EMBO journal
Publication Date
Jul 01, 1992
Volume
11
Issue
7
Pages
2487–2494
Identifiers
PMID: 1378393
Source
Medline
License
Unknown

Abstract

CFTR, the protein defective in cystic fibrosis is regulated during differentiation of intestinal epithelial cells. The undifferentiated cells (Caco-2 and HT-29) show a lower level of CFTR mRNA, while a 10-fold increase is seen in differentiated cells. These differences correlate well with those of other intestinal-specific genes, including sucrase-isomaltase, villin and alpha 1-antitrypsin, indicating that the regulation is cell specific. In Caco-2 cells the increase in CFTR mRNA cannot be accounted for by increased transcription of the gene. These data indicate that CFTR mRNA stabilizing factor(s) might be present in differentiated cells. The higher levels of CFTR mRNA in differentiated cells are accompanied by decreased protein levels, indicating, as well, involvement of translational control in the regulation of CFTR in these cells. Finally, fully differentiated cells show lowered levels of cyclic AMP-activated C1- transport, the characteristic function of CFTR. Thus, CFTR function in differentiated cells is modulated by a complex interaction of regulatory elements. Caco-2 and HT-29 cells provide a suitable in vitro system in which to study the mechanism of regulation of CFTR.

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