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Cervar-Zivkovic, M; Dieber-Rotheneder, M; Barth, S; Hahn, T; Kohnen, G; Huppertz, B; Lang, U; Desoye, G.
Endothelin-1 stimulates proliferation of first-trimester trophoblasts via the A- and B-type receptor and invasion via the B-type receptor.
J Clin Endocrinol Metab. 2011; 96(11): 3408-3415. [OPEN ACCESS]
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Autor/innen der Med Uni Graz:
Barth Sonja
Cervar-Zivkovic Mila
Desoye Gernot
Dieber-Rotheneder Martina
Hahn Tom
Huppertz Berthold
Lang Uwe
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Abstract:
Context: Endothelin-1 (ET-1) stimulates proliferation and invasion of first-trimester human trophoblast cells. Objective: To test the hypothesis that ET-1 effects are mediated by different receptor subtypes [ET receptor (ETR)-A and ETR-B]. Design: The location of ETR in trophoblast cell columns (wk 6-12) was investigated by immunohistochemistry and autoradiography. Trophoblasts were isolated from first-trimester human placentas and proliferative and invasive subpopulations separated using an integrin alpha 6 antibody. Cells were incubated for 24 h with 10 mu M ET-1 and different ETR antagonists: PD142893 (unselective), BQ-610 (ETR-A), and RES-701-1 (ETR-B). After ETR down-regulation by antisense oligonucleotides, proliferation (thymidine incorporation, protein synthesis) and invasion (Matrigel invasion) were measured. ETR expression in isolated cells was analyzed by Western blotting and semiquantitative RT-PCR. Results: Both ETR are expressed in both subpopulations in the cell column with predominance of ETR-A in the proximal part and proliferative subpopulation, whereas ETR-B is present at similar levels in both subpopulations. These results were confirmed at the mRNA level. ET-1 increased proliferation (maximum 267% of control) and invasion (maximum 288% of control) of first-trimester trophoblasts. The mitogenic ET-1 effect was inhibited (P < 0.05) by 40-80% with each receptor antagonist and by 44 and 40%, respectively, by ETR-A and ETR-B antisense oligonucleotides. The invasion-promoting effect was almost completely blocked in the presence of the ETR-B antagonists. Conclusion: The effect of ET-1 on cell proliferation in first-trimester trophoblasts is mediated by both ETR, whereas its effect on invasion is mediated predominantly by ETR-B. These effects are in line with the receptor subtype location. (J Clin Endocrinol Metab 96: 3408-3415, 2011)
Find related publications in this database (using NLM MeSH Indexing)
Cell Movement - drug effects
Cell Proliferation - drug effects
Down-Regulation - drug effects
Endothelin-1 - pharmacology
Female -
Humans -
Placenta - drug effects Placenta - metabolism
Pregnancy -
Pregnancy Trimester, First -
RNA, Messenger - metabolism
Receptor, Endothelin A - metabolism
Receptor, Endothelin B - metabolism
Trophoblasts - drug effects Trophoblasts - metabolism

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