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- Author: Jean-Jacques Feige x
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Institut National de la Santé et de la Recherche Médicale, Commissariat à l'Energie Atomique, Université Joseph Fourier, Unité 878, Grenoble, France
Institut National de la Santé et de la Recherche Médicale, Commissariat à l'Energie Atomique, Université Joseph Fourier, Unité 878, Grenoble, France
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Institut National de la Santé et de la Recherche Médicale, Commissariat à l'Energie Atomique, Université Joseph Fourier, Unité 878, Grenoble, France
Institut National de la Santé et de la Recherche Médicale, Commissariat à l'Energie Atomique, Université Joseph Fourier, Unité 878, Grenoble, France
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Institut National de la Santé et de la Recherche Médicale, Commissariat à l'Energie Atomique, Université Joseph Fourier, Unité 878, Grenoble, France
Institut National de la Santé et de la Recherche Médicale, Commissariat à l'Energie Atomique, Université Joseph Fourier, Unité 878, Grenoble, France
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Institut National de la Santé et de la Recherche Médicale, Commissariat à l'Energie Atomique, Université Joseph Fourier, Unité 878, Grenoble, France
Institut National de la Santé et de la Recherche Médicale, Commissariat à l'Energie Atomique, Université Joseph Fourier, Unité 878, Grenoble, France
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Institut National de la Santé et de la Recherche Médicale, Commissariat à l'Energie Atomique, Université Joseph Fourier, Unité 878, Grenoble, France
Institut National de la Santé et de la Recherche Médicale, Commissariat à l'Energie Atomique, Université Joseph Fourier, Unité 878, Grenoble, France
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Endocrine gland-derived vascular endothelial growth factor (EG-VEGF) and its homolog Bombina variegata (Bv8), also termed prokineticin-1 and -2 (PK1 and PK2) respectively, are newly identified peptides with specific mitogenic activity on endocrine gland-derived endothelial cells. In the present study, we analyzed the sites of expression of EG-VEGF/PK1, Bv8/PK2, and their receptors (PKR1 and PKR2) in the adrenal cortex and checked for new biological functions of these factors on the endocrine cell compartment. RT-PCR and immunostaining analyses revealed that glomerulosa and fasciculata cells express both factors and both receptors. EG-VEGF/PK1 had no effect on the steroidogenic activity of both bovine glomerulosa and fasciculata cells but appeared to be mitogenic for both cell types. Binding of EG-VEGF/PK1 to fasciculata cells stimulated the phosphorylation of ERK1/2. Pretreatment with pertussis toxin suppressed this effect, indicating that it was Gi mediated. EG-VEGF/PK1 also increased the phosphorylation of Akt in endocrine cells of the adrenal cortex. EG-VEGF/PK1 and Bv8/PK2 thus represent new regulatory peptides acting as autocrine mitogens for endocrine cells.
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Adiponectin is an adipokine with insulin-sensitizing, anti-inflammatory, anti-atherogenic, and anti-proliferative effects. The expression of specific adiponectin receptors in the placenta and in the endometrium suggests a role for this cytokine in placental development, but this role has not yet been elucidated. The invasion of trophoblast cells during the first trimester of pregnancy being crucial to placentation process, we have studied adiponectin effects on human trophoblast invasive capacities. We found that adiponectin stimulated human trophoblast cell migration in HTR-8/SVneo cells in a dose-independent manner. In addition, adiponectin also significantly enhanced invasion of HTR-8/SVneo cells and of human extravillous trophoblast from first trimester placenta. These pro-invasive effects of adiponectin in human trophoblasts seem to be mediated in part via increased matrix metalloproteinases (MMP2 and MMP9) activities and via repression of TIMP2 mRNA expression. Our results suggest that adiponectin could be a positive regulator of the early invasion process by modulating the MMP/TIMP balance. Moreover, these results provide an insight into the role of adiponectin in pathological conditions characterized by insufficient or excessive trophoblast invasion.
