Bicarbonate Transport in Cystic Fibrosis and Pancreatitis
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 <i>CFTR</i> cause fibrosis of the pancreas in utero, CFTR mutants with...
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-12-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/11/1/54 |
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| author | Dora Angyal Marcel J. C. Bijvelds Marco J. Bruno Maikel P. Peppelenbosch Hugo R. de Jonge |
| author_facet | Dora Angyal Marcel J. C. Bijvelds Marco J. Bruno Maikel P. Peppelenbosch Hugo R. de Jonge |
| author_sort | Dora Angyal |
| collection | DOAJ |
| description | 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 <i>CFTR</i> cause fibrosis of the pancreas in utero, CFTR mutants with residual function, or CFTR variants with a normal chloride but defective bicarbonate permeability (CFTR<sup>BD</sup>), 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. |
| first_indexed | 2024-03-10T03:46:14Z |
| format | Article |
| id | doaj.art-401100de1853472ba3be0b360ac851f1 |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-10T03:46:14Z |
| publishDate | 2021-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-401100de1853472ba3be0b360ac851f12023-11-23T11:19:28ZengMDPI AGCells2073-44092021-12-011115410.3390/cells11010054Bicarbonate Transport in Cystic Fibrosis and PancreatitisDora Angyal0Marcel J. C. Bijvelds1Marco J. Bruno2Maikel P. Peppelenbosch3Hugo R. de Jonge4Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center Rotterdam, P.O. Box 2040, 3000 CA Rotterdam, The NetherlandsDepartment of Gastroenterology and Hepatology, Erasmus MC University Medical Center Rotterdam, P.O. Box 2040, 3000 CA Rotterdam, The NetherlandsDepartment of Gastroenterology and Hepatology, Erasmus MC University Medical Center Rotterdam, P.O. Box 2040, 3000 CA Rotterdam, The NetherlandsDepartment of Gastroenterology and Hepatology, Erasmus MC University Medical Center Rotterdam, P.O. Box 2040, 3000 CA Rotterdam, The NetherlandsDepartment of Gastroenterology and Hepatology, Erasmus MC University Medical Center Rotterdam, P.O. Box 2040, 3000 CA Rotterdam, The NetherlandsCFTR, 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 <i>CFTR</i> cause fibrosis of the pancreas in utero, CFTR mutants with residual function, or CFTR variants with a normal chloride but defective bicarbonate permeability (CFTR<sup>BD</sup>), 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.https://www.mdpi.com/2073-4409/11/1/54CFTRcystic fibrosispancreatitisbicarbonate |
| spellingShingle | Dora Angyal Marcel J. C. Bijvelds Marco J. Bruno Maikel P. Peppelenbosch Hugo R. de Jonge Bicarbonate Transport in Cystic Fibrosis and Pancreatitis Cells CFTR cystic fibrosis pancreatitis bicarbonate |
| title | Bicarbonate Transport in Cystic Fibrosis and Pancreatitis |
| title_full | Bicarbonate Transport in Cystic Fibrosis and Pancreatitis |
| title_fullStr | Bicarbonate Transport in Cystic Fibrosis and Pancreatitis |
| title_full_unstemmed | Bicarbonate Transport in Cystic Fibrosis and Pancreatitis |
| title_short | Bicarbonate Transport in Cystic Fibrosis and Pancreatitis |
| title_sort | bicarbonate transport in cystic fibrosis and pancreatitis |
| topic | CFTR cystic fibrosis pancreatitis bicarbonate |
| url | https://www.mdpi.com/2073-4409/11/1/54 |
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