| Research Abstract |
We have recently cloned cDNA of a new human mesangium-predominant gene, megsin, which is a novel member of the serpin superfamily. The purpose of this study was to investigate the mechanisms of mesangial cell-dependent expression of this gene. The megsin gene was localized in chromosome 18q21.3, close to the other serpin genes. The gene spanned 20 kbp, and the genomic structure of the serpin superfamily was highly conserved. The sequence analysis demonstrated a consensus promoter segment within the 5^1-flanking region. Reporter assays in various cell types demonstrated strong promoter activity of this region in mesangial cells. We identified two positive regulatory elements, utilizing deletion mutagenesis and site-directed mutagenesis analysis. Electrophoretic mobility shift assays showed two unidentified transcription factors that bind to the -129 to -88 region. These transcription factors were predominantly expressed in mesangial cells. In Conclusion, high levels of megsin in mesangial cells could be explained by dominant expression of the transcription factors. Detection of the important cis-elements in the promoter and demonstration of these transcription factors in mesangial cells encourage us to perform further studies of this gene for understanding of mesangium-predominant gene expression.
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