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New insights into the pathogenesis of cystic fibrosis
M Sinaasappel1, H J Veeze, H R De Jonge
1Dept. of Pediatrics, Subdivision Gastroenterology, University Hospital Rotterdam, The Netherlands.
Insights
Cystic fibrosis (CF) research reveals abnormal ion transport in the intestines. Despite normal second messengers, potassium is secreted instead of chloride, impacting CF patient health.
Area of Science:
- Medical Genetics
- Gastroenterology
- Cell Physiology
Background:
- Cystic fibrosis (CF) is a frequent, lethal inherited childhood disease.
- High viscosity of secretions causes organ damage; improved treatments enhance prognosis.
- Recent genetic discoveries and ion transport insights are revolutionizing CF diagnosis and treatment.
Purpose of the Study:
- To investigate ion transport mechanisms in the small and large intestines of cystic fibrosis patients.
- To understand the role of intracellular signal transduction in CF-related intestinal dysfunction.
Main Methods:
- Studied ion transport in intestinal tissues from CF patients.
- Analyzed intracellular signal transfer pathways, including cAMP, cGMP, and Ca2+.
- Investigated electrolyte secretion in response to secretagogues.
Main Results:
- Intracellular signal transfer effects were abnormal in CF intestinal epithelia.
- Second messengers (cAMP, cGMP, Ca2+) were present but ineffective.
- Potassium (K+) secretion was observed instead of chloride (Cl-) secretion upon secretagogue addition.
Conclusions:
- CF intestinal ion transport is significantly impaired.
- Abnormal electrolyte secretion contributes to CF pathophysiology.
- Further research into CF ion channel function is warranted.
Abstract:
Cystic fibrosis (CF) is the most frequent inheritable disease with a lethal course during childhood. The characteristic high viscosity of the mucoid secretion products in the lungs, pancreas, and gut cause plugging and secondary damage of these organs. In the past 20 years effective treatment of intestinal obstruction in the neonatal period and the infections of the lungs has improved the prognosis significantly. Many patients will reach adulthood in the near future. In the past 10 years new insights into the cause of the disease changed diagnostic procedures and, it is to be hoped, soon also treatment. The first development was the estimation of brush-border enzymes in amniotic fluid. With this method prenatal diagnosis is possible in the 17th-18th week of pregnancy. The recent discovery of the gene on chromosome 7 and its structure is the most important breakthrough. At the same time the process of Cl- transport across the mucosal membrane of many types of epithelium was subject to investigation by several laboratories. We have studied the transport of ions in the small and large intestines of CF patients. The effect of all three types of intracellular signal transfer is abnormal, although the second messengers themselves (cAMP, cGMP, and Ca2+) are present. Evidence is found for K+ instead of Cl- secretion after addition of secretagogues.