Rein

Résumé

Le 'rein' est un organe de l'appareil urinaire des vertébrés. Il a de multiples fonctions : hormonales, de régulation de la pression sanguine et d'élimination des toxines. Il assure ainsi, par filtration et excrétion d'urine, l'équilibre hydroélectrolytique (homéostasie) du sang et de l'organisme en général. Ses fonctions hormonales comprennent la synthèse de l'érythropoïétine, du calcitriol (forme active de la vitamine D) et de la rénine. Chez les amniotes, il est le plus souvent pair et situé dans l'abdomen, dans le rétropéritoine, suivant une symétrie plus ou moins bilatérale. Il est de taille et de conformation très variable en fonction des espèces : lisses chez les humains, lobulés chez les ruminants, diffus chez les oiseaux... Par abus de langage, le langage courant nomme souvent « reins » la zone des vertèbres lombaires (ex.: « tour de reins » pour parler de lombalgie). Ambivalence La fonction complexe de cet organe vital a peut-être suscité l'ambivalence de sa ré

Source officielle

https://fr.wikipedia.org/wiki/Rein

À propos de ce résultat

Cette page est générée automatiquement et peut contenir des informations qui ne sont pas correctes, complètes, à jour ou pertinentes par rapport à votre recherche. Il en va de même pour toutes les autres pages de ce site. Veillez à vérifier les informations auprès des sources officielles de l'EPFL.

Publications associées (31)

Publications associées

Chargement

Personnes associées (4)

Personnes associées

Chargement

Unités associées (2)

Unités associées

Chargement

Concepts associés (203)

Concepts associés

Chargement

Cours associés (20)

Cours associés

Chargement

Séances de cours associées (27)

Séances de cours associées

Chargement

Renal Fanconi Syndrome and Hypophosphatemic Rickets in the Absence of Xenotropic and Polytropic Retroviral Receptor in the Nephron

Camille Ansermet, Dmitri Firsov, Vladimir Katanaev

Tight control of extracellular and intracellular inorganic phosphate (Pi) levels is critical to most biochemical and physiologic processes. Urinary Pi is freely filtered at the kidney glomerulus and is reabsorbed in the renal tubule by the action of the apical sodium -dependent phosphate transporters, NaPi-11a/NaPi-11c/Pit2. However, the molecular identity of the protein(s) participating in the basolateral Pi efflux remains unknown. Evidence has suggested that xenotropic and polytropic retroviral receptor 1 (XPR1) might be involved in this process. Here, we show that conditional inactivation of Xpr1 in the renal tubule in mice resulted in impaired renal Pi reabsorption. Analysis of Pi transport in primary cultures of proximal tubular cells or in freshly isolated renal tubules revealed that this Xpr1 deficiency significantly affected Pi efflux. Further, mice with conditional inactivation of Xpr1 in the renal tubule exhibited generalized proximal tubular dysfunction indicative of Fanconi syndrome, characterized by glycosuria, aminoaciduria, calciuria, and albuminuria. Dramatic alterations in the renal transcriptome, including a significant reduction in NaPi-lla/NaPi-llc expression, accompanied these functional changes. Additionally, Xpr1-deficient mice developed hypophosphatemic rickets secondary to renal dysfunction. These results identify XPR1 as a major regulator of Pi homeostasis and as a potential therapeutic target in bone and kidney disorders.

Amer Soc Nephrology2017

Chargement

Genetic disorders known as ciliopathies develop polycystic kidneys, including autosomal dominant and autosomal recessive polycystic kidney diseases (ADPKD and ARPKD). Several signaling pathways including the cAMP/PKA pathway are implicated in driving cystic growth. However, the mechanisms underlying cysts formation is still elusive. Renal cysts also arise in patients and in mouse models with mutations in the RNA-binding protein Bicaudal-C (Bicc1). Bicc1 binds specific mRNAs such as adenylate cyclase VI (AC6) mRNA for translational repression. Conducting a structure-function analysis, we demonstrated that Bicc1 self-polymerizes through its sterile alpha motif (SAM domain) to form cytoplasmic clusters, which specifically localize and silence bound mRNAs. Altered glucose and lipid metabolism also sustain cystic growth in polycystic kidneys, but the cause of these perturbations is unclear. Here, we found that Bicc1 is essential for normal expression of the gluconeogenic enzymes FBP1 and PEPCK specifically in kidneys, and to maintain euglycemia. In a proteomic interactome screen using a knock-in cell line, we found that TAP-tagged Bicc1 binds the C-Terminal to Lis-Homology domain (CTLH) complex, the mammalian orthologue of the glucose-induced degradation (Gid) complex that triggers degradation of FBP1 in S. cerevisiae. Bicc1 stimulates FBP1 expression in vitro in cultured murine inner medullary collecting duct (mIMCD3) cells, albeit independently of its interaction with the CTLH complex. Instead, Bicc1 and CTLH complex seem to mutually downregulate each other. Bicc1 interactome is also enriched with metabolic related proteins. Here we found that Bicc1 coimmunoprecipitates with rate-limiting metabolic enzymes and contributes to maintain their protein levels, and that deletion of Bicc1 significantly alters the renal metabolome while enhances autophagy. Altogether, these results implicate Bicc1 as an important metabolic regulator in the etiology of polycystic kidneys.

EPFL2017

Chargement

Uropathogenic Escherichia coli (UPEC) are the most common bacterial pathogens causing urinary tract infections (UTIs). Driven by the development of antibiotic resistant UPEC strains, UTIs have become a major public health issue and generate substantial healthcare costs. Even in the absence of antibiotic resistance, UTIs are notoriously difficult to treat and have high rates of recurrence, mostly due to: 1. the ability of UPEC to adhere to and invade bladder epithelial cells, which protects them from the action of antimicrobial agents and the immune system 2. the presence in antibiotic-susceptible UPEC populations of a small fraction of so-called persister cells, which are killed at a slower rate than the bulk of the population and can therefore survive prolonged antibiotic exposureThese two features allow some bacteria to remain viable in a protected niche for the whole duration of the antibiotic treatment, potentially leading to infection relapse when the treatment is terminated.High-content screening (HCS), which uses microscopy as a screening tool, allows the visualization of bacterial phenotypes at the single-cell level and can therefore provide a powerful and unbiased tool to understand the genetic basis of these phenotypes. The present thesis describes two complementary high-content screening approaches aimed at identifying UPEC mutants with altered adhesion to bladder cells and with altered antibiotic persistence respectively.In a first chapter, we report preparatory steps that led to the construction of a transposon insertion library of UPEC mutants that is suitable for high-content imaging, using the CFT073 clinical UTI isolate as background strain.In the second chapter, we performed fluorescence microscopy-based high-content screening to identify mutants with defects in early adhesion to bladder epithelial cells. We recovered 82 mutants with decreased adhesion and 54 mutants with increased adhesion. Unexpectedly, nine low-adhesion ÂÂhitsÂÂ mapped to the two P pili operons encoded by CFT073, which are thought to mediate adhesion to kidney cells rather than bladder cells. Additionally, six high-adhesion hits mapped to the operon coding for F1C pili, and we show that this phenotype is linked to increased P pili synthesis. These results therefore reveal a critical role for P pili in UPEC adhesion to bladder epithelial cells, which may inform the development of novel anti-adhesion therapies to prevent UTI recurrence.In the third chapter, we combined microfluidics with time-lapse microscopy to identify mutants with altered persistence to fosfomycin (FOS) âÂÂ a cell-wall inhibitor used as first-line agent in the treatment of UTIs âÂÂ in synthetic human urine (SHU), which mimics the physiology of UPEC in real urine. We recovered four mutants with decreased persistence, three of which had defects in lipopolysaccharide (LPS) synthesis. These results identify the outer membrane of UPEC as a key component for survival to FOS treatment, thus opening up new avenues in the fight against antibiotic persistence.

EPFL2022

Chargement

EPFL2017

EPFL2022