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Bilban, M; Ghaffari-Tabrizi, N; Hintermann, E; Bauer, S; Molzer, S; Zoratti, C; Malli, R; Sharabi, A; Hiden, U; Graier, W; Knöfler, M; Andreae, F; Wagner, O; Quaranta, V; Desoye, G.
Kisspeptin-10, a KiSS-1/metastin-derived decapeptide, is a physiological invasion inhibitor of primary human trophoblasts.
J CELL SCI. 2004; 117(Pt 8): 1319-1328.
Doi: 10.1242/jcs.00971
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- Leading authors Med Uni Graz
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Desoye Gernot
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Ghaffari Tabrizi-Wizsy Nassim
- Co-authors Med Uni Graz
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Graier Wolfgang
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Hiden Ursula
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Malli Roland
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- Abstract:
- Trophoblast invasion of the uterine extracellular matrix, a critical process of human implantation and essential for fetal development, is a striking example of controlled invasiveness. To identify molecules that regulate trophoblast invasion, mRNA signatures of trophoblast cells isolated from first trimester (high invasiveness) and term placentae (no/low invasiveness) were compared using U95A GeneChip microarrays yielding 220 invasion/migration-related genes. In this 'invasion cluster', KiSS-1 and its G-protein-coupled receptor KiSS-1R were expressed at higher levels in first trimester trophoblasts than at term of gestation. Receptor and ligand mRNA and protein were localized to the trophoblast compartment. In contrast to KiSS-1, which is only expressed in the villous trophoblast, KiSS-1R was also found in the extravillous trophoblast, suggesting endocrine/paracrine activation mechanisms. The primary translation product of KiSS-1 is a 145 amino acid polypeptide (Kp-145), but shorter kisspeptins (Kp) with 10, 13, 14 or 54 amino acid residues may be produced. We identified Kp-10, a dekapeptide derived from the primary translation product, in conditioned medium of first trimester human trophoblast. Kp-10, but not other kisspeptins, increased intracellular Ca(2+) levels in isolated first trimester trophoblasts. Kp-10 inhibited trophoblast migration in an explant as well as transwell assay without affecting proliferation. Suppressed motility was paralleled with suppressed gelatinolytic activity of isolated trophoblasts. These results identified Kp-10 as a novel paracrine/endocrine regulator in fine-tuning trophoblast invasion generated by the trophoblast itself.
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Gene Expression - chemistry
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- Find related publications in this database (Keywords)
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invasion
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DNA microarray
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kisspeptins
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metastin
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trophoblast