Human placental Hofbauer cells express sprouty proteins: a possible modulating mechanism of villous branching.
The development of the chorionic villous tree into a complex and organized ramified tubular network can be termed branching morphogenesis. Studying the molecular mechanisms involved in this process may contribute to the understanding of pregnancy complications such as preeclampsia. Sprouty (Spry) proteins are important regulators of branching morphogenesis and growth factor signaling. We analyzed the expression of Spry genes in human placenta. RT-PCR and immunohistochemistry were employed to detect placental Spry expression. Quantitative RT-PCR was used to assess the effect of FGF and reduced oxygen fraction on Spry gene expression. Spry 1, 2 and 3 expression was observed in placental tissue from all three trimesters. Our results reveal for the first time that Spry proteins are localized in the stroma of the chorionic villi, adjacent to cytotrophoblasts in areas of villous sprouting. Immunofluorescent double staining with anti-Spry and anti-CD68 confirmed that placental macrophages (Hofbauer cells) express Spry. Reduced oxygen fraction, FGF-4 and FGF-10 stimulated Spry-2 expression. Hofbauer cells also expressed c-Cbl, a protein that interacts with Spry. Placental expression of Spry and c-Cbl implies an important role for Hofbauer cells in placental development, possibly through a mesenchymal-epithelial interaction with trophoblasts. Regulation of Spry-2 expression by FGF-4 and FGF-10 suggests an orchestrated regulatory system that modulates villous branching.
Anteby
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EY
Department of Obstetrics and Gynecology, Hadassah-Hebrew University Medical Center, Mt Scopus, Jerusalem, Israel. anteby@cc.huji.ac.il
Natanson-Yaron
S
S
Greenfield
C
C
Goldman-Wohl
D
D
Haimov-Kochman
R
R
Holzer
H
H
Yagel
S
S
D002478:Cells, Cultured; D002824:Chorionic Villi / Q000502:physiology*; D005260:Female; D051526:Fibroblast Growth Factor 10; D051519:Fibroblast Growth Factor 4; D005346:Fibroblast Growth Factors / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects / Q000502:physiology; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008264:Macrophages / Q000187:drug effects / Q000502:physiology; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D010100:Oxygen / Q000494:pharmacology; D010750:Phosphoproteins / Q000235:genetics* / Q000378:metabolism; D010920:Placenta / Q000166:cytology* / Q000502:physiology*; D011247:Pregnancy; D011261:Pregnancy Trimester, First; D011262:Pregnancy Trimester, Second; D011263:Pregnancy Trimester, Third; D011506:Proteins / Q000235:genetics / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000494:pharmacology
C496463:FGF10 protein, human; C496445:FGF4 protein, human; D051526:Fibroblast Growth Factor 10; D051519:Fibroblast Growth Factor 4; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D010750:Phosphoproteins; D011506:Proteins; D011518:Proto-Oncogene Proteins; C486055:SPRY1 protein, human; C485561:SPRY2 protein, human; C407225:SPRY3 protein, human; D005346:Fibroblast Growth Factors; D010100:Oxygen