Researchers are hopeful new understanding of cellular defects related to Cystic Fibrosis (CF) could help pave the way for treatment of the disease.
A research team found that sodium transport is abnormal in lungs with CF. The researchers, studied the swine model of CF and used a specialized microelectrode technique that allowed them to perform experiments with very high resolution. They discovered there is excessive sodium absorption in the small airways, a previously unstudied site in the body.
“A precise understanding of the cellular basis of CF lung disease is a prerequisite for the development of treatments such as gene therapy that have the potential to cure CF,” said the author. “CFTR modulators, such as Trikafta, can improve life for about 90 per cent of patients. Our work is especially relevant to that 10 per cent of people with CF who cannot benefit from these medications.” Their findings were published in the journal Cell Reports.
The authors show that, under unstimulated control conditions, WT and CF epithelia exhibit similar, low rates of Na+ transport that are unaffected by the ENaC blocker amiloride.
However, in the presence of the cyclic AMP (cAMP)-elevating agents forskolin+IBMX (isobutylmethylxanthine), folds of WT tissues secrete large amounts of Na+, while CFTR−/− tissues absorb small, but potentially important, amounts of Na+.
In cAMP-stimulated conditions, amiloride inhibits Na+ absorption in CFTR−/− tissues but does not affect secretion in WT tissues. The results are consistent with the hypothesis that ENaC-mediated Na+ absorption may contribute to dehydration of CF distal airways.
https://news.usask.ca/articles/research/2021/usask-research,-published-in-major-journal,-contributes-to-understanding-of-cystic-fibrosis.php
https://www.cell.com/cell-reports/fulltext/S2211-1247(21)01255-9
http://sciencemission.com/site/index.php?page=news&type=view&id=publications%2Fcamp-triggers-na&filter=22
Reason for dehydration of cystic fibrosis distal airways
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