HOMEOBOX 1.3 EXPRESSION - INDUCTION BY RETINOIC ACID IN HUMAN BRONCHIAL FIBROBLASTS

Homeobox (Hox) genes code for transcriptional factors and are expressed during many developmental and differentiative processes. In this study, we describe the induction of Hox 1.3 expression by retinoic acid (RA) in human bronchial fibroblasts (HBF) derived from explants of bronchial tissue. Using Northern blot analysis, we show that RA induces Hox 1.3 mRNA 3- to 10-fold over steady-state levels within 2 h after addition of RA to HBF culture medium. The induction was dose dependent, reaching a half-maximal level at approximately 10(-8) M RA. This induction was not seen in human dermal fibroblasts. Immunofluorescent staining of HBF showed a corresponding increase in Hox 1.3 protein levels in the nuclei. The increase in Hox 1.3 transcript levels in HBF was not abolished by cycloheximide treatment, suggesting that synthesis of a protein intermediate is not required for the induction. RA did not significantly alter the rate of degradation of the Hox 1.3 mRNA as determined by actinomycin D treatment, suggesting that the increase in Hox 1.3 mRNA may be due to an increase in the rate of transcription. This study provides further evidence that bronchial fibroblasts are targets for RA. Although downstream target genes for Hox 1.3 have not yet been identified, it is likely that the induction of Hox 1.3 by RA is an early step in a cascade of RA-induced changes in gene expression in bronchial fibroblasts.