CFTR structure and function: is there a role in the kidney?

Abstract

Cystic fibrosis (CF) is a lethal autosomal recessive genetic disease caused by mutations in the CF transmembrane conductance regulator (CFTR). Mutations in the CFTR gene may result in a defective protein processing that leads to changes in function and regulation of this chloride channel. Despite of the expression of CFTR in the kidney, patients with CF do not present major renal dysfunction, but it is known that both the urinary excretion of proteins and renal capacity to concentrate and dilute urine are altered in these patients. CFTR mRNA is expressed in all nephron segments of rat and human, and this abundance is more prominent in renal cortex and outer medulla renal areas. CFTR protein was detected in apical surface of both proximal and distal tubules of rat kidney but not in the outer medullary collecting ducts. Studies have demonstrated that CFTR does not only transport Cl but also ATP. ATP transport by CFTR could be involved in the control of other ion transporters such as Na (ENaC) and K (renal outer medullary potassium) channels, especially in TAL and CCD. In the kidney, CFTR also might be involved in the endocytosis of low-molecular-weight proteins by proximal tubules. This review is focused on the CFTR function and structure, its role in the renal physiology, and its modulation by hormones involved in the control of extracellular fluid volume.

Precision toxicology shows that troxerutin alleviates ochratoxin A–induced renal lipotoxicity

“…Considering the role of chloride in cell swelling that contributes to membrane injury in renal epithelial cells (96), we decided to investigate the relevance of CLC regulators to nephrotoxicity and therapy. Although the role of CLCs in renal physiology is not clear (97), excessive amounts of chlorine aggravate cell damage. The shikonin in the herbal medicine is said to be a CLC inhibitor (98).…”

Purinergic signalling in the kidney in health and disease

“…In the macula densa, for example, ATP transport across the basolateral membrane is mediated by maxi-anion channels [22] and contributes to tubuloglomerular feedback (see above). CFTR channels may also mediate ATP release in the kidney [348], but this has not received firm support [296].…”

The Hypertonic Environment Differentially Regulates Wild-type CFTR and TNR-CFTR Chloride Channels

“…The cystic fibrosis transmembrane conductance regulator protein (CFTR) is an ABC (ATP-binding cassette) transporter [1]. This protein was first identified as a chloride channel but it can also function as a conductance regulator of other channels such as ENaC and ROMK [2][3][4][5].…”

“…Mutations in the CFTR gene cause disorder in secretory epithelia of the lungs, pancreas, liver, epididymis and sweat ducts, leading to a genetic disease called cystic fibrosis (CF). Although CFTR is expressed abundantly in the kidney [1], CF is not associated with major renal dysfunction perhaps suggesting that CFTR's function is redundant in the kidney.…”