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Macrophage-colony stimulating factor (M-CSF) regulates the expression of fibronectin and its alpha5 integrin receptor
A Omigbodun1, G Coukos, P Ziolkiewicz
1Department of Obstetrics and Gynecology, and the Center for Research in Reproduction and Women's Health, University of Pennsylvania, Philadelphia 19104, USA.
Abstract:
Macrophage-colony stimulating factor (M-CSF, CSF-1) is secreted by human trophoblasts as well as endometrial cells, while its receptor c-fms is abundantly expressed by the extravillous trophoblasts anchoring the placenta to the uterus, suggesting a role for M-CSF at the maternal-fetal interface. We investigated the effect of M-CSF on the expression of fibronectin and its receptor, the alpha5 integrin, in human trophoblasts. Exposure of trophoblasts to M-CSF produced a two to three-fold increase in fibronectin and alpha5 mRNA abundance at both 24 and 72 hours of culture. A dose-dependent increase in cellular fibronectin secretion into the culture medium was detected at both time points. Immunocytochemistry showed co-localization of cellular fibronectin and alpha5 in the cells, suggesting that attachment of trophoblasts to fibronectin is mediated in part by the alpha5beta1 integrin. We conclude that M-CSF increases fibronectin expression and secretion by the human trophoblasts, and up-regulates its specific receptor, the alpha5 integrin. We hypothesize that M-CSF may partake in the autocrine/paracrine mechanisms regulating trophoblast invasion during implantation.
Insights
Macrophage-colony stimulating factor (M-CSF) increases fibronectin and alpha5 integrin expression in human trophoblasts. This suggests M-CSF plays a role in placental implantation and trophoblast invasion.
Area of Science:
- Reproductive biology
- Cell biology
- Biochemistry
Background:
- Macrophage-colony stimulating factor (M-CSF) and its receptor c-fms are present at the maternal-fetal interface.
- M-CSF is secreted by trophoblasts and endometrial cells, with c-fms expressed on extravillous trophoblasts.
Purpose of the Study:
- To investigate the effect of M-CSF on fibronectin and alpha5 integrin expression in human trophoblasts.
- To explore the potential role of M-CSF in regulating trophoblast functions during implantation.
Main Methods:
- Human trophoblasts were cultured and exposed to M-CSF.
- Fibronectin and alpha5 integrin mRNA and protein levels were measured using quantitative assays.
- Immunocytochemistry was employed to visualize the localization of fibronectin and alpha5.
Main Results:
- M-CSF exposure led to a 2-3 fold increase in fibronectin and alpha5 mRNA abundance.
- A dose-dependent increase in fibronectin secretion into the culture medium was observed.
- Immunocytochemistry confirmed co-localization of fibronectin and alpha5 within trophoblasts.
Conclusions:
- M-CSF significantly increases fibronectin expression and secretion in human trophoblasts.
- M-CSF up-regulates the expression of its specific receptor, the alpha5 integrin.
- M-CSF may be involved in autocrine/paracrine signaling pathways that regulate trophoblast invasion during implantation.