title: Matrix metalloproteinase 9 is a distal-less 3 target-gene in placental trophoblast cells.
abstract: 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.
authors: Department of Biomedical Sciences, Cornell University, Ithaca, New York 14853, USA.
authors: Patricia A
authors: PA
authors: Clark
authors: Jianjun
authors: J
authors: Xie
authors: Sha
authors: S
authors: Li
authors: Xuesen
authors: X
authors: Zhang
authors: Scott
authors: S
authors: Coonrod
authors: Mark S
authors: MS
authors: Roberson
mesh_terms: D000818:Animals; D015153:Blotting, Western; D045744:Cell Line, Tumor; D002822:Choriocarcinoma / Q000378:metabolism; D005260:Female; D018093:Gelatinases / Q000235:genetics / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology*; D055785:Gene Knockdown Techniques; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D011485:Protein Binding; D034741:RNA, Small Interfering; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014327:Trophoblasts / Q000166:cytology* / Q000201:enzymology
chemical_list: C088334:Distal-less homeobox proteins; D018398:Homeodomain Proteins; D034741:RNA, Small Interfering; D014157:Transcription Factors; D018093:Gelatinases; D020780:Matrix Metalloproteinase 9
keywords: distal-less 3; human; matrix metalloproteinase; mouse; placental trophoblast
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