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Université de Fribourg

In vivo nuclear translocation of mineralocorticoid and glucocorticoid receptors in rat kidney: differential effect of corticosteroids along the distal tubule

Ackermann, Daniel ; Gresko, Nikolay ; Carrel, Monique ; Loffing-Cueni, Dominique ; Habermehl, Daniel ; Gomez-Sanchez, Celso ; Rossier, Bernard C. ; Loffing, Johannes

In: American Journal of Physiology - Renal Physiology, 2011, vol. 299, no. 6, p. F1473-F1485

Aldosterone and corticosterone bind to mineralocorticoid (MR) and glucocorticoid receptors (GR), which, upon ligand binding, are thought to translocate to the cell nucleus to act as transcription factors. Mineralocorticoid selectivity is achieved by the 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2) that inactivates 11β-hydroxy glucocorticoids. High expression levels of 11β-HSD2...

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

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

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,...

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

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

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, no. 46, p. 38264-38270

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...

Université de Fribourg

αENaC mediated lithium absorption promotes nephrogenic diabetes insipidus

Mønster Christensen, Birgitte ; Mercier Zuber, Annie ; Loffing, Johannes ; Stehle, Jean-Christophe ; Deen, Peter M.T. ; Rossier, Bernard C. ; Hummler, Edith

In: Journal of the American Society of Nephrology, 2010, vol. 21, p. -

Lithium-induced nephrogenic diabetes insipidus (NDI) is accompanied by polyuria, downregulation of aquaporin 2 (AQP2), and cellular remodeling of the collecting duct (CD). The amiloride-sensitive epithelial sodium channel (ENaC) is a likely candidate for lithium entry. Here, we subjected transgenic mice lacking αENaC specifically in the CD (knockout [KO] mice) and littermate controls to chronic...

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...