Journal de la Societe de biologie最新文献

Angiotensin II AT1 receptor is a G protein coupled receptor, which transduces the physiological effects (vasoconstriction, aldosterone secretion) f this vasoactive peptide. On an evolutionary point of view, this receptor has appeared early in the development of vertebrates, since it is present in cartilagenous fish. It has been duplicated in rodents without any consequence on its functions. It is unlikely that the angiotensin AT2 receptor, whose functions are still debated, has diverged from a common ancestral angiotensin receptor with the AT1 receptor. Numerous activating or inactivating point mutations have been identified by site-directed mutagenesis of the AT1 receptor sequence. However, such natural mutations do not appear to be frequent in the genesis of human diseases or in the diversity of phenotypic traits.

The endothelium is a tissue with a distinct identity due to the specific expression of molecular markers by endothelial cells. Further, the endothelium displays a structural heterogeneity illustrated by the expression of specific markers in arteries and in veins. Here, we present a review of the transcriptional and epigenetic mechanisms regulating the expression of the main markers of endothelial cells in man and mouse, demonstrating that there is no common and unique mechanism of specific expression of genes in these cells.

The formation of the vascular system is an early step in organogenesis that involves the participation of various signalling pathways. Integration of the extracellular signals decoded by their cognate membrane receptors orchestrate the cell events, which act at different stages, from the primitive network formed by vasculogenesis to the arborescent network remodeled by angiogenesis. Our laboratory showed the participation of a new signalling pathway in physiological angiogenesis and tumour neovascularisation. This signalling pathway named apelin comprises a G protein-coupled receptor and a peptide ligand. Expression of apelin receptors is observed during the embryonic formation of blood vessels where it is localized in the endothelium. In HUVECs, which endogenously express apelin receptors, apelin promotes the phosphorylation of ERKs, Akt and p70 S6 Kinase. In addition, apelin increases in vitro the proliferation of these endothelial cells. Finally, injection of apelin in the vitreous induces in vivo the sprouting and the proliferation of endothelial cells from the retinal vascular network. Accordingly, all these results led us to study the role of apelin signalling in tumour neovascularisation. In two tumoral cell lines, we showed that hypoxia induces the expression of apelin gene. In addition, the overexpression of apelin gene resulting from stable transfection of these cell lines clearly accelerates in vivo tumour growth, as a consequence of an increased number of vessels irrigating these tumours. The pathological relevance of these data has been validated by the characterization of an overexpression of apelin gene in one third of human tumours. Taken together, apelin signalling is both involved in physiological angiogenesis and pathological neoangiogenesis, and therefore represents an interesting pharmacological target for anti-angiogenic therapies.

Injection of endothelial progenitor cells (EPC) expanded ex vivo has been shown to increase neovascularization in preclinical models of ischemia and in adult patients, but the precise origin and identity of the cell population responsible for these clinical benefits are controversial. Given the potential usefulness of EPC as a cell therapy product, their thorough characterization is of major importance. This review describes the two cell populations currently called EPC and the means to find differential phenotypic markers. We have shown that BMP2/4 are specific markers of late EPC and play a key role in EPC commitment and outgrowth during neovascularization. Several authors have attempted to expand EPC ex vivo in order to obtain a homogeneous cell therapy product. One possible mean of expanding EPC ex vivo is to activate the thrombin receptor PAR-1 with the specific peptide SFLLRN. Indeed, PAR-1 activation increases angiogenic properties of EPC through activation of SDF-1, angiopoietin and IL-8 pathways. This review summarizes the characterization of EPC and different methods of ex vivo expansion.

This talk, given as an introduction to a symposium organised to honor André Calas, calls forth his personality, recalls the major events in his career and summarizes the evolution of his research.

Claude Bernard presented most of his fundamental results to the Société de Biologie, including proof of the modulation of the nervous system by the internal micromilieu. However, he did not describe the principle of a stable internal milieu as a condition for free life. Physiology, which is a part of biology, was not founded on cellular biology. Rather, Claude Bernard considered chemistry, anatomy and histology as the necessary auxiliary sciences for physiology. His articles are direct pictures, and not isolated ones, despite possible limitations, from a pre-montage movie of the physiological revolution he thought he had initiated, but not finished.

Intra-aortic haematopoiesis is a transient phenomenon, characterised by the emergence of Hematopoietic Stem Cells (HSC) from the ventral aortic endothelium through an endothelial cell (EC) to HSC lineage switch. HSC differentiation is followed by the colonization of definitive haematopoietic organs. Since intra-aortic haematopoiesis is born from EC of the aortic floor, we wondered how vascular integrity was maintained during hematopoietic production. We have used interspecific quail to chick grafts to study the aortic morphogenesis during hematopoiesis. We have demonstrated that: 1) before haematopoiesis, the aortic endothelium, originally entirely from splanchnic origin, was colonized by somitic EC, creating a new roof and sides derived from the somite, whereas the floor was contributed by splanchnopleural-derived EC. 2) As haematopoiesis proceeded, somite-derived EC colonized the aortic floor, where they settled underneath the HSC clusters. 3) After haematopoiesis, splanchnopleural ECs have disappeared from the aortic floor and have been replaced by somite-derived EC. At this stage, the whole aortic endothelium originated from somitic cells. 4) We have identified that the somite contributed to the vascular smooth muscle cells (VSMC). 5) Using grafts of either single quail dermomyotome or sclerotome in the chick, we showed that EC originated from the dermomyotome whereas the vascular smooth muscle cells originated from the sclerotome. Taken together, our results bring about new insights on aorta morphogenesis and the time-restricted production of HSCs.

In contrast to other vertebrates, in which the adult brain shows limited adult neurogenesis, teleost fish exhibit an unparalleled capacity to generate new neurons as adults, suggesting that their brains present a highly permissive environment for the maintenance and proliferation of adult progenitors. Here, we examine the hypothesis that one of the factors permitting establishment of this favourable environment is estradiol. Indeed, recent data showed that radial glial cells strongly expressed one of two aromatase duplicated genes. Aromatase is the estrogen-synthesizing enzyme and this observation is of great interest, given that radial glial cells are progenitor cells capable of generating new neurons. Given the well documented roles of estrogens on cell fate, and notably on cell proliferation, these data suggest that estradiol could be involved in maintaining and/or activating these progenitors. Examination of recent data in birds and mammals suggests that the situation in fish could well be an exaggeration of a more general mechanism implicating estrogens in neurogenesis. Indeed, there is accumulating evidence that estrogens are involved in embryonic, adult or reparative neurogenesis in other vertebrates, notably in mammals.