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  1. Article ; Online: IL-15 Prevents Renal Fibrosis by Inhibiting Collagen Synthesis

    Aurore Devocelle / Lola Lecru / Sophie Ferlicot / Thomas Bessede / Jean-Jacques Candelier / Julien Giron-Michel / Hélène François

    International Journal of Molecular Sciences, Vol 22, Iss 11698, p

    A New Pathway in Chronic Kidney Disease?

    2021  Volume 11698

    Abstract: Chronic kidney disease (CKD), secondary to renal fibrogenesis, is a public health burden. The activation of interstitial myofibroblasts and excessive production of extracellular matrix (ECM) proteins are major events leading to end-stage kidney disease. ... ...

    Abstract Chronic kidney disease (CKD), secondary to renal fibrogenesis, is a public health burden. The activation of interstitial myofibroblasts and excessive production of extracellular matrix (ECM) proteins are major events leading to end-stage kidney disease. Recently, interleukin-15 (IL-15) has been implicated in fibrosis protection in several organs, with little evidence in the kidney. Since endogenous IL-15 expression decreased in nephrectomized human allografts evolving toward fibrosis and kidneys in the unilateral ureteral obstruction (UUO) model, we explored IL-15’s renoprotective role by pharmologically delivering IL-15 coupled or not with its soluble receptor IL-15Rα. Despite the lack of effects on myofibroblast accumulation, both IL-15 treatments prevented tubulointerstitial fibrosis (TIF) in UUO as characterized by reduced collagen and fibronectin deposition. Moreover, IL-15 treatments inhibited collagen and fibronectin secretion by transforming growth factor-β (TGF-β)-treated primary myofibroblast cultures, demonstrating that the antifibrotic effect of IL-15 in UUO acts, in part, through a direct inhibition of ECM synthesis by myofibroblasts. In addition, IL-15 treatments resulted in decreased expression of monocyte chemoattractant protein 1 (MCP-1) and subsequent macrophage infiltration in UUO. Taken together, our study highlights a major role of IL-15 on myofibroblasts and macrophages, two main effector cells in renal fibrosis, demonstrating that IL-15 may represent a new therapeutic option for CKD.
    Keywords chronic kidney disease ; fibrosis ; unilateral ureteral obstruction ; interleukin-15 ; myofibroblasts ; extracellular matrix ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
    Subject code 616
    Language English
    Publishing date 2021-10-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  2. Article ; Online: Circulating CASK is associated with recurrent focal segmental glomerulosclerosis after transplantation.

    Severine Beaudreuil / Xiaomeng Zhang / Florence Herr / Francis Harper / Jean Jacques Candelier / Ye Fan / Hilal Yeter / Caroline Dudreuilh / Lola Lecru / Aime Vazquez / Bernard Charpentier / Hans K Lorenzo / Antoine Durrbach

    PLoS ONE, Vol 14, Iss 7, p e

    2019  Volume 0219353

    Abstract: Introduction Focal and Segmental GlomeruloSclerosis (FSGS) can cause nephrotic syndrome with a risk of progression to end-stage renal disease. The idiopathic form has a high rate of recurrence after transplantation, suggesting the presence of a systemic ... ...

    Abstract Introduction Focal and Segmental GlomeruloSclerosis (FSGS) can cause nephrotic syndrome with a risk of progression to end-stage renal disease. The idiopathic form has a high rate of recurrence after transplantation, suggesting the presence of a systemic circulating factor that causes glomerular permeability and can be removed by plasmapheresis or protein-A immunoadsorption. Results To identify this circulating factor, the eluate proteins bound on therapeutic immunoadsorption with protein-A columns were analyzed by comparative electrophoresis and mass spectrometry. A soluble form of calcium/calmodulin-dependent serine protein kinase (CASK) was identified. CASK was immunoprecipitated only in the sera of patients with recurrent FSGS after transplantation and not in control patients. Recombinant-CASK (rCASK) induced the reorganization of the actin cytoskeleton in immortalized podocytes, a redistribution of synaptopodin, ZO-1,vinculin and ENA. rCASK also induced alterations in the permeability of a monolayer of podocytes and increased the motility of pdodocytes in vitro. The extracellular domain of CD98, a transmembrane receptor expressed on renal epithelial cells, has been found to co-immunoprecipitated with rCASK. The invalidation of CD98 with siRNA avoided the structural changes of rCask treated cells suggesting its involvement in physiopathology of the disease. In mice, recombinant CASK induced proteinuria and foot process effacement in podocytes. Conclusion Our results suggest that CASK can induce the recurrence of FSGS after renal transplantation.
    Keywords Medicine ; R ; Science ; Q
    Subject code 610
    Language English
    Publishing date 2019-01-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  3. Article ; Online: Genome-wide high-resolution aCGH analysis of gestational choriocarcinomas.

    Henriette Poaty / Philippe Coullin / Jean Félix Peko / Philippe Dessen / Ange Lucien Diatta / Alexander Valent / Eric Leguern / Sophie Prévot / Charles Gombé-Mbalawa / Jean-Jacques Candelier / Jean-Yves Picard / Alain Bernheim

    PLoS ONE, Vol 7, Iss 1, p e

    2012  Volume 29426

    Abstract: Eleven samples of DNA from choriocarcinomas were studied by high resolution CGH-array 244 K. They were studied after histopathological confirmation of the diagnosis, of the androgenic etiology and after a microsatellite marker analysis confirming the ... ...

    Abstract Eleven samples of DNA from choriocarcinomas were studied by high resolution CGH-array 244 K. They were studied after histopathological confirmation of the diagnosis, of the androgenic etiology and after a microsatellite marker analysis confirming the absence of contamination of tumor DNA from maternal DNA. Three cell lines, BeWo, JAR, JEG were also studied by this high resolution pangenomic technique. According to aCGH analysis, the de novo choriocarcinomas exhibited simple chromosomal rearrangements or normal profiles. The cell lines showed various and complex chromosomal aberrations. 23 Minimal Critical Regions were defined that allowed us to list the genes that were potentially implicated. Among them, unusually high numbers of microRNA clusters and imprinted genes were observed.
    Keywords Medicine ; R ; Science ; Q
    Language English
    Publishing date 2012-01-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

    Full text online

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    Inter-library loan at ZB MED

    Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

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