Inhibition of TGF-alpha gene expression by vitamin A in airway epithelium.
The autocrine/paracrine growth mechanism has been implicated in the regulation of bronchial epithelial cell proliferation. By inhibiting the expression of the transforming growth factor-alpha (TGF-alpha) gene product, vitamin A is able to suppress the proliferation of tracheobronchial epithelial cells in culture. Similar repressions in TGF-alpha mRNA levels by retinol were observed in airway explant cultures and in a cell line immortalized from normal human bronchial epithelial cells. Both the nuclear run-on transcriptional assay and the transfection study with the chimeric construct of the TGF-alpha promoter and chloramphenicol acetyltransferase reporter gene partly suggest a transcriptional downregulation mechanism of TGF-alpha gene expression by the retinol treatment; however, this inhibition at the transcriptional level cannot account for the total inhibition at the mRNA level. These results suggest that a downregulation of the expression of the TGF-alpha gene at the transcriptional and post-transcriptional levels by vitamin A may precede the essential event associated with the homeostasis of normal conducting airway epithelium.
Miller
L A
LA
California Regional Primate Research Center, University of California at Davis, 95616, USA.
Zhao
Y H
YH
Wu
R
R
D000818:Animals; D001483:Base Sequence; D005786:Gene Expression Regulation / Q000187:drug effects*; D000882:Haplorhini; D006801:Humans; D008969:Molecular Sequence Data; D012137:Respiratory System / Q000378:metabolism*; D016211:Transforming Growth Factor alpha / Q000096:biosynthesis / Q000235:genetics*; D014801:Vitamin A / Q000494:pharmacology*
D016211:Transforming Growth Factor alpha; D014801:Vitamin A