Role of CFTR and ClC-5 in Modulating Vacuolar H&lt;sup&gt;+&lt;/sup&gt;-ATPase Activity in Kidney Proximal Tubule

Carraro‐Lacroix, Luciene Regina; Lessa, Lucília Maria Abreu; Bezerra, Camila Nogueira Alves; Pessoa, Thaíssa Dantas; Souza-Menezes, Jackson; Morales, Marcelo M.; Girardi, Adriana C. C.; Malnic, Gerhard

doi:10.1159/000322324

Cited by 24 publications

(13 citation statements)

References 59 publications

(79 reference statements)

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“…2007; Jouret and Devuyst 2009; Carraro‐Lacroix et al. 2010). TNR‐CFTR is a splice variant form of CFTR that is far more prevalent in the kidney than the usual form.…”

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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“…2007; Jouret and Devuyst 2009; Carraro‐Lacroix et al. 2010). TNR‐CFTR is a splice variant form of CFTR that is far more prevalent in the kidney than the usual form.…”

Section: Discussionmentioning

confidence: 99%

“…2005; Carraro‐Lacroix et al. 2010). Nonetheless, functioning of the proximal tubule endocytic machinery is still poorly understood in the diabetes context.…”

Section: Introductionmentioning

confidence: 99%

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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“…In rabbit S3 proximal tubules perfused in vitro, Na + -independent pHi recovery following an acid load is dependent on intracellular Cl − (400) and the shuttling of cytoplasmic H + -ATPase containing vesicles to the apical membrane is also Cl − -dependent (477). In rat proximal tubules (superficial S1 and S2 segments), H + -ATPase activity was shown to be Cl − -dependent (830) and evidence was provided that CFTR and ClC-5 may play a role (141). …”

Section: Proximal Tubulementioning

confidence: 99%

Molecular Mechanisms and Regulation of Urinary Acidification

Kurtz

2014

Comprehensive Physiology

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The H+ concentration in human blood is kept within very narrow limits, ~ 40 nM, despite the fact that dietary metabolism generates acid and base loads that are added to the systemic circulation throughout the life of mammals. One of the primary functions of the kidney is to maintain the constancy of systemic acid-base chemistry. The kidney has evolved the capacity to regulate blood acidity by performing three key functions: 1) reabsorb HCO3− that is filtered through the glomeruli to prevent its excretion in the urine; 2) generate a sufficient quantity of new HCO3− to compensate for the loss of HCO3− resulting from dietary metabolic H+ loads and loss of HCO3− in the urea cycle; and 3) excrete HCO3− (or metabolizable organic anions) following a systemic base load. The ability of the kidney to perform these functions requires that various cell types throughout the nephron respond to changes in acid-base chemistry by modulating specific ion transport and/or metabolic processes in a coordinated fashion such that the urine and renal vein chemistry is altered appropriately. The purpose of the article is to provide the interested reader with a broad review of a field that began historically ~ 60 years ago with whole animal studies, and has evolved to where we are currently addressing questions related to kidney acid-base regulation at the single protein structure/function level.

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“…-ATPase was thought to be the main function of the channel [57,58]. Recent evidence shows that the role of ClC-5 during endocytosis is the modulation of chloride concentration during proton transport, rather than acidification [59,60]. A small fraction of ClC-5 is also present on the apical surface of proximal tubular cells and may play a role in proteinprotein interactions since it interacts with cofilin, NHERF2, and KIF3B, all required for receptor-mediated endocytosis [61,62].…”

Section: Dent Diseasementioning

confidence: 99%