Cystic Fibrosis Is Associated with a Defect in Apical Receptor–Mediated Endocytosis in Mouse and Human Kidney

Jouret, François; Bernard, Alfred; Hermans, Cédric; Dom, Geert; Terryn, Sara; Leal, Teresinha; Lebecque, Patrick; Cassiman, Jean Jacques; Scholte, Bob Bj; Jonge, Hugo R. de; Courtoy, Pierre J.; Devuyst, Olivier

doi:10.1681/asn.2006030269

Cited by 91 publications

(100 citation statements)

References 44 publications

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“…A previous work from Jouret et al. (2007) also highlighted the association of higher urinary transferrin excretion with CFTR downregulation. These authors found a greater amount of transferrin in the urine of patients with cystic fibrosis, a genetic disease that is characterized by CFTR dysfunction (Jouret et al.…”

Section: Discussionmentioning

confidence: 97%

“…2001; Jentsch 2005; Jouret et al. 2007; Souza‐Menezes et al. 2007; Jouret and Devuyst 2009; Carraro‐Lacroix et al.…”

Section: Discussionmentioning

confidence: 99%

“…These authors found a greater amount of transferrin in the urine of patients with cystic fibrosis, a genetic disease that is characterized by CFTR dysfunction (Jouret et al. 2007). Also, this increase in urinary excretion of transferrin was observed in ClC‐5 KO mice (Christensen et al.…”

Section: Discussionmentioning

confidence: 99%

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Diabetic rats present higher urinary loss of proteins and lower renal expression of megalin, cubilin, ClC-5, and CFTR

et al. 2017

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Diabetic nephropathy (DN) occurs in around 40% of those with diabetes. Proteinuria is the main characteristic of DN and develops as a result of increased permeability of the glomerulus capillary wall and/or decreased proximal tubule endocytosis. The goal of this work was to evaluate renal function and the expression of megalin, cubilin, CFTR (cystic fibrosis transmembrane conductance regulator), and ClC‐5 in the proximal tubule and renal cortex of rats with type 1 diabetes. Male Wistar rats were randomly assigned to control (CTRL) and diabetic (DM) groups for 4 weeks. Renal function was assessed in 24‐h urine sample by calculating clearance and fractional excretion of solutes. The RNA and protein contents of ClC‐5, CFTR, megalin, and cubilin were determined in the renal proximal tubule and cortex using real‐time polymerase chain reaction and western blotting techniques, respectively. The results showed higher creatinine clearance and higher urinary excretion of proteins, albumin, and transferrin in the DM group than in the CTRL group. Furthermore, the renal cortex and proximal tubule of diabetic animals showed downregulation of megalin, cubilin, ClC‐5, and CFTR, critical components of the endocytic apparatus. These data suggest dysfunction in proximal tubule low‐molecular‐weight endocytosis and protein glomerulus filtration in the kidney of diabetic rats.

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Section: Discussionmentioning

confidence: 97%

“…2001; Jentsch 2005; Jouret et al. 2007; Souza‐Menezes et al. 2007; Jouret and Devuyst 2009; Carraro‐Lacroix et al.…”

Section: Discussionmentioning

confidence: 99%

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Diabetic rats present higher urinary loss of proteins and lower renal expression of megalin, cubilin, ClC-5, and CFTR

et al. 2017

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“…It is probably involved in proximal tubule receptormediated endocytosis. Inactivation of CFTR leads to detection of significant, although variable, low molecular weight proteinuria in patients with CF (4). Nonetheless, there is no overt clinically relevant renal phenotype in children or teenagers with CF; however, asymptomatic nephrocalcinosis and hypercalciuria are present in up to 90 and 30% of individuals with CF, respectively (5).…”

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confidence: 99%

Renal Involvement in Cystic Fibrosis

Yahiaoui¹,

Jablonski²,

Hubert³

et al. 2009

Clinical Journal of the American Society of Nephrology

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Background and objectives: Clinically relevant kidney involvement is uncommonly described in adult patients with cystic fibrosis (CF). We sought to report on a series of patients with CF and kidney biopsy-documented renal involvement.Design, setting, participants, & measurements: A retrospective study was undertaken in two referral centers for adult patients with CF in Paris, France. Patients who had undergone a biopsy of native kidneys between 1992 and 2008 were identified, and their medical records were reviewed.Results: We identified 13 adult patients with CF and renal disease. Proteinuria was present in all but two cases and was associated with progressive renal impairment in four patients (median serum creatinine 85 mol/L; range 53 to 144 mol/L). Renal biopsy disclosed a heterogeneous spectrum of nephropathies including AA amyloidosis (n ‫؍‬ 3), diabetic glomerulopathy (n ‫؍‬ 3), FSGS (n ‫؍‬ 2), minimal-change disease (n ‫؍‬ 1), postinfectious glomerulonephritis (n ‫؍‬ 1), IgA nephropathy related to Henoch-Schö nlein purpura (n ‫؍‬ 1), membranous nephropathy (n ‫؍‬ 1), and chronic interstitial nephropathy (n ‫؍‬ 1). Chronic renal failure occurred in five patients, and one patient reached ESRD. Conclusions: Although rare, clinically significant renal disease may arise in young adult patients with CF. Given the wide spectrum of diseases that may be encountered, definite diagnosis by kidney biopsy is mandatory to optimize clinical treatment of these complex patients, particularly in the perspective of organ transplantation.

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“…RT-PCR detection was performed with platinum TaqDNA polymerase (Invitrogen) for 32 cycles, and PCR products were visualized on a 1.5% agarose gel. Real-time quantitative PCR analyses were performed in duplicate by using iQ SYBR Green Supermix (Bio-Rad, Hercules, CA) (40). PCR conditions were 94°C for 3 min followed by 40 cycles of 30 s at 95°C, 30 s at 61°C, and 1 min at 72°C.…”

mentioning

confidence: 99%

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

Belge¹,

Gailly²,

Schwaller

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

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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 Ca 2؉ -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 (Pvalb ؊/؊ ) vs. wild-type (Pvalb ؉/؉ ) littermates. PV colocalized with the thiazidesensitive Na ؉ -Cl ؊ cotransporter (NCC) in the early DCT. The Pvalb ؊/؊ mice showed increased diuresis and kaliuresis at baseline with higher aldosterone levels and lower lithium clearance. Acute furosemide administration increased diuresis and natriuresis/kaliuresis, but, surprisingly, did not increase calciuria in Pvalb ؊/؊ mice. NaCl supplementation of Pvalb ؊/؊ mice increased calciuria at baseline and after furosemide. The Pvalb ؊/؊ mice showed no significant diuretic response to hydrochlorothiazide, but an accentuated hypocalciuria. A decreased expression of NCC was detected in the early DCT of Pvalb ؊/؊ kidneys in the absence of ultrastructural and apoptotic changes. The PV-deficient mice had a positive Ca 2؉ balance and increased bone mineral density. Studies in mouse DCT cells showed that endogenous NCC expression is Ca 2؉ -dependent and can be modulated by the levels of PV expression. These results suggest that PV regulates the expression of NCC by modulating intracellular Ca 2؉ signaling in response to ATP in DCT cells. They also provide insights into the Ca 2؉ -sparing action of thiazides and the pathophysiology of distal tubulopathies.distal convoluted tubule ͉ kidney ͉ salt-losing nephropathy ͉ sodium-chloride cotransport P arvalbumin (PV) belongs to the superfamily of EF-hand Ca 2ϩ -binding proteins that play a role in multiple cellular processes, including gene transcription, ion transport, protein phosphorylation, and enzymatic activities (1). These proteins possess well conserved helix-loop-helix motifs that bind Ca 2ϩ ions with high affinity, leading to conformational changes. The conformational plasticity and the cell-specific expression of these Ca 2ϩ sensor or buffer proteins contribute to the versatility of Ca 2ϩ signaling (2). PV is a 109-aa cytosolic protein that contains a pair of functional EF-hand motifs forming a stable unit that binds two Ca 2ϩ ions (3). This Ca 2ϩ buffer is expressed in a restricted number of vertebrate tissues, including fast-contracting/relaxing skeletal muscle fibers and GABA neurons in the brain (4). The generation of PV knockout (Pvalb Ϫ/Ϫ ) mice confirmed the important role played by PV in muscle and brain (5). The fast muscles of Pvalb Ϫ/Ϫ mice exhibit a decreased relaxation rate of the twitch (5), suggesting that PV facilitates Ca 2ϩ diffusion from myofibrils to the sarcoplasmic reticulum (6). The lack of PV in the brain induces changes in short-term synaptic plasticity and modified network properties, resulting in increased susceptibility to epileptic seizures (7). Although no human disease is ass...

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Cystic Fibrosis Is Associated with a Defect in Apical Receptor–Mediated Endocytosis in Mouse and Human Kidney

Cited by 91 publications

References 44 publications

Diabetic rats present higher urinary loss of proteins and lower renal expression of megalin, cubilin, ClC-5, and CFTR

Diabetic rats present higher urinary loss of proteins and lower renal expression of megalin, cubilin, ClC-5, and CFTR

Renal Involvement in Cystic Fibrosis

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

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