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Université de Fribourg

Mouse model of type II Bartter's syndrome. II. Altered expression of renal sodium- and water-transporting proteins

Wagner, Carsten A. ; Loffing-Cueni, Dominique ; Yan, Qingshang ; Schulz, Nicole ; Fakitsas, Panagiotis ; Carrel, Monique ; Wang, Tong ; Verrey, François ; Geibel, John P. ; Giebisch, Gerhard ; Hebert, Steven C. ; Loffing, Johannes

In: American Journal of Physiology: Renal Physiology, 2008, vol. 294, no. 6, p. F1373-F1380

ROMK-deficient (Romk–/–) mice exhibit polyuria, natriuresis, and kaliuresis similar to individuals with type II Bartter's form of hyperprostaglandin E syndrome (HPS; antenatal Bartter's syndrome). In the present study, we utilized both metabolic and clearance studies to define the contributions of specific distal nephron segments to the renal salt wasting in these mice. The...

Université de Fribourg

Renal expression of parvalbumin is critical for NaCl handling and response to diuretics

Belge, Hendrica ; Gailly, Philippe ; Schwaller, Beat ; Loffing, Johannes ; Debaix, Huguette ; Riveira-Munoz, Eva ; Beauwens, Renaud ; Devogelaer, Jean-Pierre ; Hoenderop, Joost G. ; Bindels, René J. ; Devuyst, Olivier

In: Proceedings of the National Academy of Sciences of the United States of America, 2007, vol. 104, no. 37, p. 14849-14854

The distal convoluted tubule (DCT) plays an essential role in the reabsorption of NaCl by the kidney, a process that can be inhibited by thiazide diuretics. Parvalbumin (PV), a Ca²⁺-binding protein that plays a role in muscle fibers and neurons, is selectively expressed in the DCT, where its role remains unknown. We therefore investigated the renal phenotype of PV knockout mice...

Université de Fribourg

Replication of segment-specific and intercalated cells in the mouse renal collecting system

Wehrli, Philipp ; Loffing-Cueni, Dominique ; Kaissling, Brigitte ; Loffing, Johannes

In: Histochemistry and Cell Biology, 2007, vol. 127, no. 4, p. 389-398

The renal collecting system (CS) is composed of segment-specific (SS) and intercalated (IC) cells. The latter comprise at least two subtypes (type A and non-type A IC). The origin and maintenance of cellular heterogeneity in the CS is unclear. Among other hypotheses, it was proposed that one subtype of IC cells represents a stem cell population from which all cell types in the CS may arise. In...

Université de Fribourg

Dietary sodium intake regulates the ubiquitin-protein ligase nedd4-2 in the renal collecting system

Loffing-Cueni, Dominique ; Flores, Sandra Y. ; Sauter, Daniel ; Daidié, Dorothée ; Siegrist, Nicole ; Meneton, Pierre ; Staub, Olivier ; Loffing, Johannes

In: Journal of the American Society of Nephrology, 2006, vol. 17, p. 1264-1274

The activity of the epithelial sodium (Na⁺) channel (ENaC) in the aldosterone-sensitive distal nephron (ASDN) needs to be tightly regulated to match urinary Na⁺ excretion with dietary Na⁺ intake. The ubiquitin-protein ligase Nedd4-2, which in vitro interacts with ENaC subunits and reduces ENaC cell surface abundance and activity by ubiquitylation of the channel, may participate in...

Université de Fribourg

Progesterone down-regulates the open probability of the amiloride-sensitive epithelial sodium channel via a Nedd4-2-dependent mechanism

Michlig, Stéphanie ; Harris, Michael ; Loffing, Johannes ; Rossier, Bernard C. ; Firsov, Dmitri

In: Journal of Biological Chemistry, 2005, vol. 280(46), p. 38264

Activation of the mitogen-activated protein (MAP) kinase cascade by progesterone in Xenopus oocytes leads to a marked down-regulation of activity of the amiloride-sensitive epithelial sodium channel (ENaC). Here we have studied the signaling pathways involved in progesterone effect on ENaC activity. We demonstrate that: (i) the truncation of the C termini of the αβγENaC subunits results...

Université de Fribourg

Functional domains of the epithelial sodium channel

Loffing, Johannes ; Schild, Laurent

In: Journal of the American Society of Nephrology, 2005, vol. 16, p. 3175

Université de Fribourg

Aldosterone-induced serum and glucocorticoid-induced kinase 1 expression is accompanied by Nedd4-2 phosphorylation and increased Na+ transport in cortical collecting duct cells

Flores, Sandra Y. ; Loffing-Cueni, Dominique ; Kamynina, Elena ; Daidié, Dorothée ; Gerbex, Carole ; Chabanel, Sting ; Dudler, Jean ; Loffing, Johannes ; Staub, Olivier

In: Journal of the American Society of Nephrology, 2005, vol. 16, p. 2279

Aldosterone plays a central role in Na⁺ homeostasis by controlling Na⁺ reabsorption in the aldosterone-sensitive distal nephron involving the epithelial Na⁺ channel (ENaC). Part of the effects of aldosterone is mediated by serum and glucocorticoid-induced kinase 1 (Sgk1), a Ser/Thr kinase whose expression is rapidly induced by aldosterone and that increases in heterologous expression...

Université de Fribourg

Enhanced passive Ca²⁺ reabsorption and reduced Mg²⁺ channel abundance explains thiazide-induced hypocalciuria and hypomagnesemia

Nijenhuis, Tom ; Vallon, Volker ; Kemp van der, Annemiete W.C.M. ; Loffing, Johannes ; Hoenderop, Joost G.J. ; Bindels, René J.M.

In: The Journal of Clinical Investigation, 2005, vol. 115(6), p. 1651

Thiazide diuretics enhance renal Na⁺ excretion by blocking the Na⁺-Cl⁻ cotransporter (NCC), and mutations in NCC result in Gitelman syndrome. The mechanisms underlying the accompanying hypocalciuria and hypomagnesemia remain debated. Here, we show that enhanced passive Ca²⁺ transport in the proximal tubule rather than active Ca²⁺ transport in distal convolution explains...

Université de Fribourg

Characterization of renal interstitial fibroblast-specific protein 1/S100A4-positive cells in healthy and inflamed rodent kidneys

Le Hir, Michel ; Hegyi, Ivan ; Cueni-Loffing, Dominique ; Loffing, Johannes ; Kaissling, Brigitte

In: Histochemistry and Cell Biology, 2005, vol. 123(4-5), p. 335

Fibrosis is considered as a central factor in the loss of renal function in chronic kidney diseases. The origin of fibroblasts and myofibroblasts that accumulate in the interstitium of the diseased kidney is still a matter of debate. It has been shown that accumulation of myofibroblasts in inflamed and fibrotic kidneys is associated with upregulation of fibroblast-specific protein 1 (FSP1,...