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Villaret A.,French Institute of Health and Medical Research | Villaret A.,University Paul Sabatier | Villaret A.,Laboratoires Serobiologiques | Galitzky J.,French Institute of Health and Medical Research | And 16 more authors.
Diabetes | Year: 2010

OBJECTIVE - Regional differences among adipose depots in capacities for fatty acid storage, susceptibility to hypoxia, and inflammation likely contribute to complications of obesity. We defined the properties of endothelial cells (EC) isolated from subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) biopsied in parallel from obese subjects. RESEARCH DESIGN AND METHODS - The architecture and properties of the fat tissue capillary network were analyzed using immunohistochemistry and flow cytometry. CD34 +/CD31+ EC were isolated by immunoselection/depletion. Expression of chemokines, adhesion molecules, angiogenic factor receptors, as well as lipogenic and senescence-related genes were assayed by real-time PCR. Fat cell size and expression of hypoxia-dependent genes were determined in adipocytes from both fat depots. RESULTS - Hypoxia-related genes were more highly expressed in VAT than SAT adipocytes. VAT adipocytes were smaller than SAT adipocytes. Vascular density and EC abundance were higher in VAT. VAT-EC exhibited a marked angiogenic and inflammatory state with decreased expression of metabolism-related genes, including endothelial lipase, GPIHBP1, and PPAR gamma. VAT-EC had enhanced expression of the cellular senescence markers, IGFBP3 and γ-H2AX, and decreased expression of SIRT1. Exposure to VAT adipocytes caused more EC senescence-associated β-galactosidase activity than SAT adipocytes, an effect reduced in the presence of vascular endothelial growth factor A (VEGFA) neutralizing antibodies. CONCLUSIONS - VAT-EC exhibit a more marked angiogenic and proinflammatory state than SAT-EC. This phenotype may be related to premature EC senescence. VAT-EC may contribute to hypoxia and inflammation in VAT. © 2010 by the American Diabetes Association.


Harfouche G.,French Atomic Energy Commission | Vaigot P.,French Atomic Energy Commission | Rachidi W.,French Atomic Energy Commission | Rachidi W.,CEA Grenoble | And 8 more authors.
Stem Cells | Year: 2010

Tissue stem cells must be endowed with superior maintenance and repair systems to ensure genomic stability over multiple generations, which would be less necessary in more differentiated cells. We previously reported that human keratinocyte stem cells were more resistant to ionizing radiation toxicity than their direct progeny, the keratinocyte progenitor cells. In the present study we addressed the mechanisms underlying this difference. Investigations of DNA repair showed that both single and double DNA strand breaks were repaired more rapidly and more efficiently in stem cells than in progenitors. As cell signaling is a key regulatory step in the management of DNA damage, a gene profiling study was performed. Data revealed that several genes of the fibroblast growth factor type 2 (FGF2) signaling pathway were induced by DNA damage in stem cells and not in progenitors. Furthermore, an increased content of the FGF2 protein was found in irradiated stem cells, both for the secreted and the cellular forms of the protein. To examine the role of endogenous FGF2 in DNA repair, stem cells were exposed to FGF2 pathway inhibitors. Blocking the FGF2 receptor (FGF receptor 1) or the kinase (Ras-mitogen-activated protein kinase 1) resulted in a inhibition of single and double DNA strand-break repair in the keratinocyte stem cells. Moreover, supplementing the progenitor cells with exogenous FGF2 activated their DNA repair. We propose that, apart from its well-known role as a strong mitogen and prosurvival factor, FGF2 helps to maintain genomic integrity in stem cells by activating stress-induced DNA repair. ©AlphaMed Press.


Trademark
Cognis France S.A. and Laboratoires Serobiologiques | Date: 2000-02-29

compounds used in the manufacture of cosmetic and personal hygiene products, namely natural, vegetal and biotechnological extracts.


Trademark
Cognis France S.A. and Laboratoires Serobiologiques | Date: 1998-03-31

compounds used in the manufacture of perfume, make-up and personal hygiene products, namely, essential oils for sale to industrial manufacturers.


Trademark
Cognis France S.A. and Laboratoires Serobiologiques | Date: 1998-01-27

compounds used in the manufacture of perfume, make-up and personal hygiene products, namely, natural, vegetal, marine, animal and synthetic extracts for sale to industrial manufacturers.

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