CFTR and defective endocytosis: new insights in the renal phenotype of cystic fibrosis.

Animals; Chloride Channels/physiology; Cystic Fibrosis/physiopathology; Cystic Fibrosis Transmembrane Conductance Regulator/genetics/physiology; Endocytosis/physiology; Humans; Kidney/physiopathology; Kidney Tubules, Proximal/physiopathology; Mice

Abstract :

[en] Inactivation of the chloride channel cystic fibrosis transmembrane conductance regulator (CFTR) causes cystic fibrosis (CF). Although CFTR is expressed in the kidney, no overwhelming renal phenotype is associated with CF. Recent studies have shown that the level of CFTR mRNA in mouse kidney approaches that found in lung. CFTR is particularly abundant in the apical area of proximal tubule cells, where it co-distributes with the Cl(-)/H(+) exchanger ClC-5 and Rab5a in endosomes. The biological relevance of CFTR in proximal tubule endocytosis has been tested in CF mouse models and CF patients. Mice lacking CFTR show a defective receptor-mediated endocytosis, as evidenced by impaired uptake of (125)I-beta(2)-microglobulin, a decreased expression of the cubilin receptor in the kidney, and a significant excretion of cubilin and its low-molecular-weight ligands into the urine. Low-molecular-weight proteinuria (and particularly transferrinuria) is similarly detected in CF patients in comparison with normal controls or patients with chronic lung inflammation. These studies suggest that the functional loss of CFTR impairs the handling of low-molecular-weight proteins by the kidney, supporting a role of CFTR in receptor-mediated endocytosis in proximal tubule cells. The selective proteinuria should be integrated in the pathophysiology of multi-systemic complications increasingly observed in CF patients.

Disciplines :

Anatomy (cytology, histology, embryology...) & physiology

Author, co-author :

JOURET, François ; Centre Hospitalier Universitaire de Liège - CHU > Néphrologie

Devuyst, Olivier

Language :

English

Title :

CFTR and defective endocytosis: new insights in the renal phenotype of cystic fibrosis.

Publication date :

2009

Journal title :

Pflügers Archiv: European Journal of Physiology

ISSN :

0031-6768

eISSN :

1432-2013

Publisher :

Springer, Berlin, Germany

Volume :

457

Issue :

Pages :

1227-36

Peer reviewed :

Peer Reviewed verified by ORBi

Available on ORBi :

since 20 November 2012

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