AJP - Cell Physiology, Vol 263, Issue 1 C55-C60, Copyright © 1992 by American Physiological Society
Expression and regulation of the cystic fibrosis gene during rat liver regeneration
R. Tran-Paterson, D. Davin, R. D. Krauss, T. A. Rado and D. M. Miller
Department of Internal Medicine, University of Alabama, Birmingham.
Mutations in the cystic fibrosis transmembrane conductance regulator (CFTR)
are responsible for cystic fibrosis. The CFTR gene has recently been
identified and encodes a 6.5-kb mRNA transcript. Recent observations
showing that CFTR expression increases during differentiation of epithelial
cells suggested that CFTR may also be regulated in the liver in response to
partial hepatectomy (PH). We studied the expression of CFTR in rat
regenerating liver and investigated the mechanisms that regulate CFTR RNA
levels during a 120-h period after PH. Northern and slot-blot analysis
revealed a liver-specific biphasic increase of CFTR mRNA levels, which
peaks at 2 and 24 h post-PH. In contrast to these findings, the mode of
regulation of the homologous gene MDR-1 showed a clearly different pattern.
Nuclear run-on analysis demonstrated increased levels of CFTR transcription
corresponding to the time points where an increase in CFTR message was
observed. Similarly, the beta-actin gene, which increases transiently
during liver regeneration, showed increased nuclear run-on activity 4 h
posthepatectomy, indicating that the nuclei were functional. No increase of
MDR-1 gene transcription was detected, confirming the previous finding that
the increase in MDR-1 mRNA level in regenerating liver results from a
post-transcriptional event such as message stabilization. This study
indicates that expression of the CFTR gene is regulated during the
regenerative process of the liver. The data also suggest that the increase
in CFTR and MDR expression levels result from two distinct regulatory
mechanisms.
