Bicarbonate transport in cystic fibrosis and pancreatitis

Dora Angyal, Marcel J.C. Bijvelds, Marco J. Bruno, Maikel P. Peppelenbosch, Hugo R. de Jonge*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

6 Citations (Scopus)
10 Downloads (Pure)

Abstract

CFTR, the cystic fibrosis (CF) gene-encoded epithelial anion channel, has a prominent role in driving chloride, bicarbonate and fluid secretion in the ductal cells of the exocrine pancreas. Whereas severe mutations in CFTR cause fibrosis of the pancreas in utero, CFTR mutants with residual function, or CFTR variants with a normal chloride but defective bicarbonate permeability (CFTRBD), are associated with an enhanced risk of pancreatitis. Recent studies indicate that CFTR function is not only compromised in genetic but also in selected patients with an acquired form of pancreatitis induced by alcohol, bile salts or smoking. In this review, we summarize recent insights into the mechanism and regulation of CFTR-mediated and modulated bicarbonate secretion in the pancreatic duct, including the role of the osmotic stress/chloride sensor WNK1 and the scaffolding protein IRBIT, and current knowledge about the role of CFTR in genetic and acquired forms of pancreatitis. Furthermore, we discuss the perspectives for CFTR modulator therapy in the treatment of exocrine pancreatic insufficiency and pancreatitis and introduce pancreatic organoids as a promising model system to study CFTR function in the human pancreas, its role in the pathology of pancreatitis and its sensitivity to CFTR modulators on a personalized basis.

Original languageEnglish
Article number54
JournalCells
Volume11
Issue number1
DOIs
Publication statusPublished - 24 Dec 2021

Bibliographical note

Funding Information:
This study was funded by the Cystic Fibrosis Foundation (CFF-USA; DEJONG19G0), the Dutch Cystic Fibrosis Foundation (NCFS; HIT-CF2) and the Fondazione Ricerca Fibrosi Cistica (FFC; #3/2016; #9/2020).The authors wish to thank Wichor Bramer from the Erasmus MC Medical Library for developing and updating the search strategies.

Funding Information:
Funding: This study was funded by the Cystic Fibrosis Foundation (CFF-USA; DEJONG19G0), the Dutch Cystic Fibrosis Foundation (NCFS; HIT-CF2) and the Fondazione Ricerca Fibrosi Cistica (FFC; #3/2016; #9/2020).

Publisher Copyright:
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.

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