| First Author | Clark PA | Year | 2013 |
| Journal | Am J Physiol Cell Physiol | Volume | 305 |
| Issue | 2 | Pages | C173-81 |
| PubMed ID | 23657566 | Mgi Jnum | J:204022 |
| Mgi Id | MGI:5529418 | Doi | 10.1152/ajpcell.00205.2012 |
| Citation | Clark PA, et al. (2013) Matrix metalloproteinase 9 is a distal-less 3 target-gene in placental trophoblast cells. Am J Physiol Cell Physiol 305(2):C173-81 |
| abstractText | Matrix metalloproteinases (MMPs) are enzymes that regulate extracellular matrix composition and contribute to cell migration. Microarray studies in mouse placenta suggested that MMP-9 transcript abundance was dependent on distal-less 3 (Dlx3), a placental-specific transcriptional regulator; however, it was not clear if this was a direct or indirect effect. Here we investigate mechanism(s) for Dlx3-dependent MMP-9 gene transcription and gelatinase activity in placental trophoblasts. Initial studies confirmed that MMP-9 activity was reduced in placental explants from Dlx3(-/-) mice and that murine MMP-9 promoter activity was induced by Dlx3 overexpression. Two binding sites within a murine MMP-9 promoter fragment bound Dlx3, and mutations in both elements reduced basal MMP-9-luciferase reporter activity and abolished regulation by Dlx3. Chromatin immunoprecipitation studies in JEG3 cells confirmed Dlx3 binding to the endogenous human MMP-9 promoter at three distinct sites and knockdown of human Dlx3 resulted in reduced endogenous MMP-9 transcripts and secreted activity. These studies provide novel evidence that Dlx3 is involved directly in the transcriptional regulation of mouse and human MMP-9 gene expression in placental trophoblasts. |
