OPPOSITE ACTIONS OF TRANSFORMING GROWTH FACTOR-BETA(1) ON THE GENE-EXPRESSION OF ATRIAL-NATRIURETIC-PEPTIDE BIOLOGICAL AND CLEARANCE RECEPTORS IN A MURINE THYMIC STROMAL CELL-LINE

The regulation of the gene expression of the atrial natriuretic peptide receptor (ANPR) subtypes, ANPR-A, ANPR-B, and ANPR-C, was investigated in a murine thymic stromal cell line, MRL 104.8a. When MRL 104.8a cells were cultured with transforming growth factor (TGF)-beta(1), [I-125]ANP binding sites increased with increasing dose of TGF-beta(1). These binding sites were identified as ANPR-C by a displacement experiment with ANPR-C-specific ligand, C-ANF, and by the affinity cross-linking of the [I-125] ANp binding sites with a chemical cross-linker to determine the molecular weight of the ANPR. This augmentation of the ANPR-C expression was elucidated to occur at the transcriptional level by Northern blot experiment, comparison of the relative amounts of mRNA by reverse transcription (RT)-PCR, and in vitro nuclear transcription assay. Conversely, the expression of the ANP biological receptors, ANPR-A and ANPR-B, was shown to be down-regulated by TGF-beta(1). These data suggest that TGF-beta(1) regulates the gene expression of ANPRs in the thymic stromal cells and that ANP and TGF-beta(1) might affect the thymic stromal cell functions.